Diagnostic autoantibody profiles for the detection and diagnosis of neurodegenerative diseases

ABSTRACT

The present invention provides methods, compositions, and kits for the detection of neurodegenerative disease specific autoantibodies for the diagnosis of neurodegenerative diseases and risk for developing neurodegenerative diseases, and for the generation of patient-specific neurodegenerative disease diagnostic autoantibody profiles.

CROSS-REFERENCE TO RELATED APPLICATION

This application is the U.S. National Phase of International PatentApplication Serial No. PCT/US11/30883, filed on Apr. 1, 2011, whichclaims the benefit of U.S. Provisional Application Nos. 61/334,466 filedMay 13, 2010 and 61/444,932 filed Feb. 21, 2011, the disclosures ofwhich are incorporated herein by reference in their entireties.

BACKGROUND OF THE INVENTION

An autoantibody is an antibody manufactured by an individual's immunesystem that is directed against an antigen of the individual's ownproteins. Antibodies are normally produced in response to a foreignprotein or substance within the body, typically a pathogen, which is aninfectious organism. Normally, the immune system is able to recognizeand ignore the body's own cells and not overreact to non-threateningsubstances in the environment, such as foods. Sometimes, however, theimmune system ceases to recognize one or more of the body's normalconstituents as “self”, leading to production of autoantibodies. Theseautoantibodies attack the body's own cells, tissues, and/or organs,causing inflammation and damage.

Serum autoantibodies have been implicated in a wide variety ofneurological diseases and syndromes. Neuron-binding autoantibodies havebeen detected in sera from individuals exhibiting obsessive compulsivedisorder, Sydenham's chorea, pediatric autoimmune neuropsychiatricdisorders associated with streptococcal infection (“PANDAS”), andHashimoto's encephalopathy. Schizophrenia has also been linked to theappearance of autoantibodies, including several directed againstneuronal surface receptors. Systemic lupus erythematosus (“SLE”), knownto be caused by antinuclear antibodies, appears to have cognitive andmemory loss components consistent with the presence of a subset ofanti-DNA antibodies that cross-react with the N-methyl-D-aspartatereceptor (“NMDAR”). Also, brain-reactive antibodies in mothers ofautistic children elicit behavioral abnormalities in progeny whenadministered to pregnant mammals.

Moreover, among neurodegenerative diseases, autoantibodies have beenfound in Parkinson's disease, Autism spectrum disorders, amyotrophiclateral sclerosis, multiple sclerosis, Guillain-Barre syndrome, chronicperipheral neuropathy, optic neuritis, vascular dementia, and Alzheimersdisease (“AD”). In the case of AD, there have been numerous reports ofpatients having high titers of autoantibodies to both non-brain andbrain-associated targets, including neuron-binding autoantibodies.Moreover, several specific autoantibody targets have been identified,including aldolase, heavy neurofilament subunit, histone, tubulin, glialfibrillary acid protein, and S-100.

Alzheimer's disease (AD) is a progressive and devastatingneurodegenerative disorder of the elderly that is highlighted by adramatic reduction of memory and cognition and linked to loss of neuronsand synapses (Selkoe (2002) Science 298, 789-91). Additional keypathological features include the deposition of amyloid beta (Aβ),especially the 42-amino acid peptide (Aβ42), within neurons, amyloidplaques and in the walls of brain blood vessels, as well as theappearance of neurofibrillary tangles, glial activation and widespreadinflammation (Schwab et al. (2008) J Alzheimers Dis 13, 359-69; Thal etal. (2008) Acta Neuropathol 115, 599-609; Weisman et al. (2006) VitamHorm 74, 505-30). Aβ42 deposition within neurons is initiated early inthe course of the disease, precedes amyloid plaque and tangle formation,and temporally and spatially coincides with loss of synapses in human ADand transgenic mouse brains (D'Andrea et al. (2001) Histopathology 38,120-134; Nagele et al. (2002) J Neurosci 110, 199-211; Gouras et al.(2000) Am J Patho. 156, 15-20). This has led to the proposal that thegradual growth of Aβ deposits may progressively impair the ability ofneurons to support their extensive dendritic arbors, therebycontributing to early synaptic loss that eventually becomes apparentthrough telltale symptoms.

Studies have reported the presence of immunoglobulin (Ig)-immunopositiveneurons in histological sections of post-mortem AD brains, which wereonly rarely observed in comparable brain regions of non-demented,age-matched controls (Stein et al. (2002) J Neuropathol Exp Neurol 61,1100-8; Bouras et al. (2005) Brain Res Brain Res Rev 48, 477-87;D'Andrea (2003) Brain Res Brain Res Rev 982, 19-30). The presence ofspecific brain-reactive autoantibodies in the serum of AD patients hasalso been reported. (Bouras et al. (2005) Brain Res Brain Res Rev 48,477-87; Kulmala et al. (1987) Exp Aging Res 13, 67-72; Mecocci et al.(1993) Biol Psychiatry 34, 380-5; Mecocci et al. (1995) J Neuroimmunol57, 165-70; Weksler et al. (2002) Exp Gerontol 37, 971-979).

Autism spectrum disorders (“ASDs”) are a group of disorders in braindevelopment that includes autism, Asperger's syndrome, Rett's disorder,and childhood disintegrative disorder. ASDs are characterized byimpairments in social behavior and communication that are usuallyexpressed within the first 36 months of childhood (American PsychiatricAssociation: Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition (2000)). A substantial fraction (20-30%) of autismpatients undergo a period of autistic regression during which theyexperience a loss of previously acquired milestones in language andbehavioral skills (Fombonne (2003) JAMA 289, 87-89). Inexplicably, theprevalence of ASD has recently increased dramatically, a finding not dueto improved diagnostics, but rather suggesting some environmental causalfactor(s). ASDs now affect 1:150 children, and the etiology is largelyunknown but likely to be multifactorial (Fombonne, 2003).

Neuropathological and neuroimaging studies of autistic patients havereported increased brain size and weight (Bailey et al. (1998) PsycholMed 25, 63-77; Kemper and Bauman (1998) Neurol Clinic 1, 175-87; Palmenet al. (2004) Brain 127, 2572-2583). Many studies of autistic brainshave reported an overall reduction in neuron size and an increasedneuron packing density, especially in the hippocampus, subiculum andamygdala (Kemper and Bauman, 1993).

ASDs have been linked to specific brain abnormalities. Neurologicalobservations and neuroimaging studies have provided evidence that manybrain regions can be affected in autism, including the cerebellum,cerebral cortex, amygdala, hippocampus, basal ganglia and the brain stem(Akshoomoff et al., 2002; Acosta and Pearl (2004) Semin Pediatr Neurol11, 205-213). Cerebellar abnormalities are also common in ASD,hallmarked by a scarcity of Purkinje and granule cells (Courchesne etal., 2001).

Autoimmunity and autoantibodies are involved in the pathogenesis of ASDs(Ashwood et al. (2006) J Leukocyte Biol 80, 1-11; Wills et al. (2007)Ann N.Y. Acad Sci 1107, 79-91; Zimmerman et al. (2007) Brain Behav Immun21, 351-357). The binding of autoantibodies to neurons can disrupt thenormal pattern of neurodevelopment at critical stages. Autoantibodiesreactive to the brain have been reported in autistic children, andseveral autoimmune factors including brain-specific autoantibodies,impaired lymphocyte function, abnormal cytokine regulation, and viralassociations have been implicated (Singh and Rivas (2004) Neurosci Lett355, 53-56). For example, Singh and Rivas (2004) have shown that theserum of autistic children contains brain-specific autoantibodies. In astudy of 68 autistic children at 4-12 years of age, antibodies to thecaudate nucleus, cerebral cortex and cerebellum were detected in 49%,18% and 9%, respectively, of autistic children, but not in normalchildren. Another study has shown that children with Tourette syndromepossess anti-striatal antibodies, and influsion of these antibodies intothe rat striatum caused neuronal dysfunction similar to Tourettesyndrome (Hallet et al. (2000) J Neuroimmunol 111, 195-202). Otheranti-brain antibodies have also been found in autistic patients,including antibodies to serotonin receptor, myelin basic protein, axonfilament protein, cerebellar neurofilaments, nerve growth factor, brainendothelial proteins and antibodies directed against other unidentifiedbrain proteins.

A strong link between the presence of anti-neuronal autoantibodies andneurological disease has been shown in children in cases followingstreptococcal infections, such as in obsessive compulsive disorder(OCD), Sydenham's chorea, Tourette syndrome, PANDAS, and paraneoplasia,and in elderly patients with SLE that show both cognitive and memoryloss (Swedo et al. (1989) Am J Psychiatry 154, 110-2; Kalume et al.(2004) J Neurosci Res 77, 82-89; Tanaka et al. (2004) J Neurological Sci217, 25-30). DeGeorgio et al. (2001) Nature Med 11, 1189-1193 and Kowalet al. (2004) Immunity 21, 179-188, report that a subset of anti-DNAantibodies in SLE patients cross-reacts with the NMDA(N-methyl-D-aspartate) subtype of glutamate receptors (NR2a and NR2b) bymeans of molecular mimicry and induces neuronal injury and death both invivo and in vitro.

SUMMARY OF THE INVENTION

In one embodiment, the present invention provides a method for detectingneurodegenerative disease diagnostic autoantibodies in a subjectcomprising obtaining a biological sample from the subject, andperforming an assay to determine the presence or absence of one or moreneurodegenerative disease diagnostic autoantibodies in the biologicalsample.

In another embodiment, the present invention provides a method fordiagnosing a neurodegenerative disease in a subject comprising obtaininga biological sample from the subject, performing an assay to determinethe presence or absence of one or more neurodegenerative diseasediagnostic autoantibodies in the biological sample, and diagnosing saidneurodegenerative disease if one or more of the disease diagnosticautoantibodies is present.

In another embodiment, the present invention provides a method ofidentifying a subject at risk for developing a neurodegenerative diseasecomprising obtaining a biological sample from the subject, performing anassay to determine the presence or absence of one or moreneurodegenerative disease diagnostic autoantibodies in the biologicalsample, and identifying the subject as at risk for developing saidneurodegenerative disease if one or more of the disease diagnosticautoantibodies is present.

In another embodiment, the present invention provides a method ofgenerating a subject-specific, neurodegenerative disease diagnosticautoantibody profile comprising obtaining a biological sample from asubject, performing an assay to determine the presence or absence of oneor more neurodegenerative disease diagnostic autoantibodies in thebiological sample, and generating a subject-specific neurodegenerativedisease diagnostic autoantibody profile of the disease diagnosticautoantibodies present in the sample.

Another embodiment of this invention provides a substrate on which oneor more autoantigens that are specific for one or more neurodegenerativedisease diagnostic autoantibodies are immobilized.

Another embodiment of this invention provides a microarray comprising asubstrate on which one or more autoantigens that are specific for one ormore neurodegenerative disease diagnostic autoantibodies areimmobilized.

Another embodiment of this invention provides a kit for detectingneurodegenerative disease diagnostic autoantibodies.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graphical representation of a diagnostic logic exemplifiedin Example 8.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with the present invention, it has been discovered thatautoantibodies, also known as self-reactive antibodies, are bothabundant and ubiquitous in human sera, regardless of age or the presenceor absence of disease. Some are brain-reactive; others are reactive totargets in other organs throughout the body. Although someautoantibodies may be vestiges of past diseases and immunologicalactivity, it has been discovered in accordance with the presentinvention that many autoantibodies are also present in the blood andcerebrospinal fluid as a result of existing or ongoing diseases. It isthis latter group that is useful for the early detection and diagnosisof existing diseases.

It has been discovered herein that the presence of activeneurodegenerative disease, including both long- and short-term diseases,causes the production and release of cellular products as a result ofcell damage related to ongoing pathology, some of which are both celltype- and organ-specific. These released cellular products (many ofwhich are proteins), their break-down fragments and disease-relatedpost-translational modifications enter the blood and lymph circulation,act as antigens, and elicit an immune response. This immune responseleads to the production and appearance of a relatively large number ofself-reactive autoantibodies in the blood. Cells throughout the bodyshare a vast number of proteins in common, but only a relatively smallsubset of autoantibodies are specifically reactive to the cells, tissuesand organs involved in a particular disease. It has been discovered inaccordance with the present invention that this response leads to adisease-specific autoantibody profile that is characteristic for eachdisease and the specific cell types involved. In addition, inindividuals with concurrent diseases, it has been discovered herein thata specific pattern of autoantibodies reflects each of these concurrent,ongoing disease processes.

Additionally, it has been discovered herein that autoantibodies capableof binding to brain-specific targets, including neurons and theirsupportive glial cells, are common in the blood; in fact they appear tobe ubiquitous. Binding of these autoantibodies to neurons and/or glialcells in the brain is harmful to these cells and the functions in whichthey participate. It not only disrupts normal cellular functions, butalso eventually leads to neuron and glial cell death and permanent lossfrom the brain.

Once inside the brain tissue, autoantibodies are free to bindselectively to any cells within the brain that possess and display theproper target antigens on their surfaces. If the autoantibody target isparticularly abundant on a cell surface, the binding of many moleculesof autoantibody can crosslink and immobilize this protein. If the targetis an important receptor, the target and the cell can be renderednonfunctional, leading to more global brain functional impairments. Whenthe target cells are neurons, autoantibody binding may lead to neuronaldysfunction that can eventually manifest itself as behavioral,cognitive, memory and motor impairments. When the target is a glial cellthat supports neurons, the loss of this support may indirectlycompromise the function of neurons. Thus, specific brain-reactiveautoantibodies in human sera can put one at risk for specificneurodegenerative diseases. The invention described herein provides amethod for the detection of these autoantibodies in human biologicalsamples.

Thus in one embodiment, the present invention provides a method ofidentifying a subject at risk for developing a neurodegenerative diseasecomprising obtaining an immunoglobulin-containing biological sample fromthe subject, performing an assay to determine the presence or absence ofone or more neurodegenerative disease diagnostic autoantibodies in thebiological sample, and identifying the subject as at risk for developingsaid neurodegenerative disease if one or more of the disease diagnosticautoantibodies is present.

In another embodiment of this invention provides a method for detectingneurodegenerative disease diagnostic autoantibodies in a subjectcomprising obtaining an immunoglobulin-containing biological sample fromthe subject, and performing an assay to determine the presence orabsence of one or more neurodegenerative disease diagnosticautoantibodies in the biological sample.

In a preferred embodiment, the neurodegenerative disease is selectedfrom the group consisting of Alzheimer's disease, Parkinson's disease,amyotrophic lateral sclerosis, multiple sclerosis, Guillain-Barresyndrome, chronic peripheral neuropathy, optic neuritis, vasculardementia, obsessive compulsive disorder, Sydenham's chorea, pediatricautoimmune neuropsychiatric disorders associated with streptococcalinfection (“PANDAS”), Hashimoto's encephalopathy, schizophrenia,systemic lupus erythematosus, vascular cognitive disorders, stroke,Huntington's disease, neuromyelitis optica, paraneoplastic syndromes,limbic encephalitis, Rasmussen encephalitis, Hashimoto's encephalitis,encephalitis lethargica, stiff person syndrome, post-streptococcalmovement disorders, rheumatic fever, gluten enteropathy, ASD, dyslexia,HTLV-1-associated myelopathy/tropical spastic paraparesis, myastheniagravis, Lambert-Eaton syndrome, and arthrogryposis multiplex congenita.

In a preferred embodiment of the invention, the subject is a human.

In a preferred embodiment of the invention, theimmunoglobulin-containing biological sample is serum, whole blood, CSF,saliva, or sputum. A blood sample may be obtained by methods known inthe art including venipuncture or a finger stick. CSF may be obtained bymethods known in the art including a lumbar spinal tap. To obtain serumfrom blood, a sample of blood is received and centrifuged at a speedsufficient to pellet all cells and platelets, and the serum to beanalyzed is drawn from the resulting supernatant. Sputum and salivasamples may be collected by methods known in the art. The biologicalsamples may be diluted with a suitable buffer.

In a preferred embodiment of the invention, the assay used to determinethe presence or absence of one or more neurodegenerative diseasediagnostic autoantibodies in the biological sample is performed bycontacting the biological sample with one or more autoantigens that arespecific for a neurodegenerative disease diagnostic autoantibody underconditions that allow an immunocomplex of the autoantigen and theautoantibody to form, and detecting the presence of the immunocomplex.

Autoantibodies that are specific for a neurodegenerative diseasediagnostic autoantibody may be identified by comparing theautoantibodies present in a immunoglobulin-containing sample from asubject having a neurodegenerative disease with autoantibodies presentin an immunoglobulin-containing sample from an age-matched disease-freecontrol subject. The target autoantigens for the autoantibodies presentin the sample from the subject having the disease but not present in thesample from the control subject provide the identification of thedisease diagnostic autoantibodies. The sample is preferably serum.

For example, protein microarrays containing thousands of full-sized ornearly full-sized human proteins spotted on a single specimen slide maybe used to identify autoantibodies in a patient sample that are reactivewith the antigen targets on the microarray. Autoantibodies in a controlsample may be similarly identified. The patient autoantibody profile maybe compared with the control autoantibody profile to determine thedisease specific autoantibodies and corresponding autoantigens.

Protein microarrays useful for identifying neurodegenerative diseasediagnostic autoantibodies and autoantigens may be made by methods knownin the art and are also commercially available. Commercially availableprotein microarrays include, for example, Invitrogen's Prot® Array®Human Protein Microarray v5.0, which is preferably used in accordancewith the Invitrogen ProtoArray® protocol and Immune Response BiomarkerProfiling application.

Methods for probing and scanning such protein microarrays, and fordetermining the diagnostic significance of the resulting data, are knownto those of skill in the art and disclosed, for example, by Tibshiraniet al. (2002) Proc Natl Acad Sci USA 99, 6567-6572. Once theautoantibodies that are diagnostic for the neurodegenerative disease areidentified by the foregoing methods, the corresponding autoantigens areidentified and selected for use in the methods of detection anddiagnosis.

An autoantigen may comprise a protein antigen, a polypeptide or peptidefragment thereof containing one or more epitopes recognized by thedisease diagnostic autoantibody, or an epitope peptidomimetic that isrecognized by the disease diagnostic autoantibody. The autoantigens maybe purified from natural sources, or produced recombinantly orsynthetically by methods known in the art, and may be in the form offusion proteins. The autoantigens may be produced in vitro usingcell-free translation systems. In one preferred embodiment, theautoantigens are produced in a mammalian or insect expression system toensure correct folding and function. All of these methods may beautomated for high throughput production.

Assays and conditions for the detection of immunocomplexes are known tothose of skill in the art. Such assays include, for example, competitionassays, direct reaction assays and sandwich-type assays. The assays maybe quantitative or qualitative. In one preferred embodiment, the assayutilizes a solid phase or substrate to which the autoantigens aredirectly or indirectly attached, such as a microtiter or microassayplate, slide, magnetic bead, non-magnetic bead, column, matrix,membrane, dipstick, filter, membrane, pin, or sheet, and may be composedof a synthetic material such as polystyrene, polyvinyl chloride,polyamide, or other synthetic polymers, natural polymers such ascellulose, derivatized natural polymers such as cellulose acetate ornitrocellulose, and glass, for example glass fibers. The substratepreferably comprises a plurality of individually addressableautoantigens immobilized on the surface. The individually addressableautoantigens are preferably immobilized on the surface to form an array.The substrates may be used in suitable shapes, such as films, sheets, orplates, or may be coated onto or bonded or laminated to appropriateinert carriers, such as paper, glass, plastic films, or fabrics. In apreferred embodiment, the substrate is a slide or a bead.

Methods for attaching the autoantigens to the support or substrate areknown in the art and include covalent and noncovalent interactions. Forexample, diffusion of applied proteins into a porous surface such ahydrogel allows noncovalent binding of unmodified protein withinhydrogel structures. Covalent coupling methods provide a stable linkageand may be applied to a range of proteins. Biological capture methodsutilising a tag (e.g., hexahistidine/Ni-NTA or biotin/avidin) on theprotein and a partner reagent immobilized on the surface of thesubstrate provide a stable linkage and bind the protein specifically andin reproducible orientation. In one preferred embodiment, theautoantigens are coated or spotted onto the support or substrate such aschemically derivatized glass. In a more preferred embodiment,nitrocellulose-coated glass slides are used

In one preferred embodiment the autoantigens are provided in the form ofan array, and preferably a microarray. Protein microarrays are known inthe art and reviewed for example by Hall et al. (2007) Mech Ageing Dev128:161-167 and Stoevesandt et al (2009) Expert Rev Proteomics6:145-157, the disclosures of which are incorporated herein by referencein their entireties. Microarrays may be prepared by immobilizingpurified autoantigens on a substrate such as a treated microscope slideusing a contact spotter or a non-contact microarrayer. Microarrays mayalso be produced through in situ cell-free synthesis directly fromcorresponding DNA arrays.

Suitable methods for external production and purification ofautoantigens to be spotted on arrays include expression in bacteria, asdisclosed for example by Venkataram et al. (2008) Biochemistry47:6590-6601, in yeast, as disclosed for example by Li et al. (2007)Appl Biochem Biotechnol. 142:105-124, in insect cells, as disclosed forexample by Altman et al. (1999) Glycoconj J 16:109-123, and in mammaliancells, as disclosed for example by Spampinato et al. (2007) Curr DrugTargets 8:137-146.

Suitable methods for in situ (“on-chip”) protein production aredisclosed, for example, by Ramachandran et al. (2006) Methods Mol. Biol.2328:1-14 and He et al. (2008) Curr. Opin Biotechnol 19:4-9.

Other methods by which proteins are simultaneously expressed andimmobilized in parallel on an array surface are also known in the artand may be used in accordance with the present invention. For example,in the Protein In Situ Arrays (PISA) method (He et al. (2001) NucleicAcids Res 29:e73), proteins are made directly from DNA, either insolution or immobilized, and become attached to the array surface asthey are made through recognition of a tag sequence. The proteins areexpressed in parallel in vitro utilizing a cell free system, commonlyrabbit reticulocyte or E. coli S30, to perform coupled transcription andtranslation. In this method, protein expression is performed on asurface which is precoated with an immobilizing agent capable of bindingto the tag. Thus after each protein is translated, it becomes fixedsimultaneously and specifically to the adjacent surface, while the othermaterials can subsequently be washed away. Microarrays may be produceddirectly onto glass slides, either by mixing the DNA with the cell freelysate system before spotting or by a multiple spotting technique (MIST)in which DNA is spotted first followed by the expression system.

In the system known as Nucleic Acid Programmable Protein Array (NAPPA)(Ramachandran et al. (2004) Science 305:86-90), transcription andtranslation from an immobilized (as opposed to a solution) DNA templateallow conversion of DNA arrays to protein arrays. In this method,biotinylated cDNA plasmids encoding the proteins as GST fusions areprinted onto an avidin-coated slide, together with an anti-GST antibodyacting as the capture entity. The cDNA array is then covered with rabbitreticulocyte lysate to express the proteins, which become trapped by theantibody adjacent to each DNA spot, the proteins thereby becomingimmobilized with the same layout as the cDNA. This technology generatesa protein array in which the immobilized proteins are present togetherwith DNA and a capture agent.

Another suitable method for generating a protein array is the DNA Arrayto Protein Array (DAPA) method. This method for in situ protein arrayinguses an immobilized DNA array as the template to generate ‘pure’ proteinarrays on a separate surface from the DNA, and also can produce multiplecopies of a protein array from the same DNA template (He et al. (2008)Nature Methods, 5:175-7). Cell-free protein synthesis is performed in amembrane held between two surfaces (e.g., glass slides), one of which isarrayed with DNA molecules while the other surface carries a specificreagent to capture the translated proteins. Individual, tagged proteinsare synthesized in parallel from the arrayed DNA, diffuse across the gapand are subsequently immobilized through interaction with thetag-capturing reagent on the opposite surface to form a protein array.Discrete spots which accurately reflect the DNA in position and quantityare produced. Replicate copies of the protein array can be obtained byreuse of the DNA.

Array fabrication methods include robotic contact printing, ink-jetting,piezoelectric spotting and photolithography. For example, purifiedautoantigens of the invention that are produced and purified externallymay be spotted onto a microarray substrate using a flexible proteinmicroarray inkjet printing system (e.g., ArrayJet, Roslin, Scotland, UK)to provide high quality protein microarray production. The precise rowsand columns of autoantigens may be converted to detectable spotsdenoting both the presence and amount of diagnostic autoantibodies thathave been bound.

The production of the microarrays is preferably performed withcommercially available printing buffers designed to maintain thethree-dimensional shape of the autoantigens. In one preferredembodiment, the substrate for the microarray is a nitrocellulose-coatedglass slide.

The assays are performed by methods known in the art in which the one ormore autoantigens are contacted with the biological sample underconditions that allow the formation of an immunocomplex of anautoantigen and an antibody, and detecting the immunocomplex. Thepresence and amount of the immunocomplex may be detected by methodsknown in the art, including label-based and label-free detection. Forexample, label-based detection methods include addition of a secondaryantibody that is coupled to an indicator reagent comprising a signalgenerating compound. The secondary antibody may be an anti-human IgGantibody. Indicator reagents include chromogenic agents, catalysts suchas enzyme conjugates, fluorescent compounds such as fluorescein andrhodamine, chemiluminescent compounds such as dioxetanes, acridiniums,phenanthridiniums, ruthenium, and luminol, radioactive elements, directvisual labels, as well as cofactors, inhibitors and magnetic particles.Examples of enzyme conjugates include alkaline phosphatase, horseradishperoxidase and beta-galactosidase. Methods of label-free detectioninclude surface plasmon resonance, carbon nanotubes and nanowires, andinterferometry. Label-based and label-free detection methods are knownin the art and disclosed, for example, by Hall et al. (2007) and by Rayet al. (2010) Proteomics 10:731-748. Detection may be accomplished byscanning methods known in the art and appropriate for the label used,and associated analytical software.

In one preferred embodiment of the present invention, fluorescencelabeling and detection methods are used to detect the immunocomplexes.Commericially available slide scanners (e.g. the Genepix 4000B slidescanner (Molecular Devices, Inc.) with associated analytical softwaremay be used. In one preferred embodiment, the immunocomplex is probedwith fluorescent-labeled (e.g., Alexa-Fluor (Invitrogen)) anti-humanantibody and the intensity of fluorescence at each protein spot ismeasured using a microarray scanner. Commercially available software(e.g. GenePix Pro 5.0 software (Axon instruments)) may be used toextract the net median pixel intensities for individual features fromthe digital images produced by the scanner. Data may be normalized bycomparing median values of multiple identical control spots in differentregions of the same array.

Detection of immunocomplexes is indicative of the presence ofneurodegenerative disease diagnostic autoantibodies in the biologicalsample, and thus a positive diagnosis of neurodegenerative disease.

Another embodiment of this invention provides a method for diagnosing aneurodegenerative disease in a subject comprising obtaining animmunoglobulin-containing biological sample from the subject, performingan assay to determine the presence or absence of one or moreneurodegenerative disease diagnostic autoantibodies in a biologicalsample, and diagnosing said disease if one or more of the diseasediagnostic autoantibodies is present.

In a preferred embodiment, the neurodegenerative disease is selectedfrom the group consisting of Alzheimer's disease, Parkinson's disease,amyotrophic lateral sclerosis, multiple sclerosis, Guillain-Barresyndrome, chronic peripheral neuropathy, optic neuritis, vasculardementia, obsessive compulsive disorder, Sydenham's chorea, PANDAS,Hashimoto's encephalopathy, schizophrenia, systemic lupus erythematosus,vascular cognitive disorders, stroke, Huntington's disease,neuromyelitis optica, paraneoplastic syndromes, limbic encephalitis,Rasmussen encephalitis, Hashimoto's encephalitis, encephalitislethargica, stiff person syndrome, post-streptococcal movementdisorders, rheumatic fever, gluten enteropathy, ASD, dyslexia,HTLV-1-associated myelopathy/tropical spastic paraparesis, myastheniagravis, Lambert-Eaton syndrome, and arthrogryposis multiplex congenita.

In a preferred embodiment of the invention, the subject is a human.

In a preferred embodiment of the invention, theimmunoglobulin-containing biological sample is serum, whole blood, CSF,saliva, or sputum. A blood sample may be obtained by methods known inthe art including venipuncture or a finger stick. CSF may be obtained bymethods known in the art including a lumbar spinal tap. To obtain serumfrom blood, a sample of blood is received and centrifuged at a speedsufficient to pellet all cells and platelets, and the serum to beanalyzed is drawn from the resulting supernatant. Sputum and salivasamples may be collected by methods known in the art. The biologicalsamples may be diluted with a suitable buffer.

In a preferred embodiment, the assay used for diagnosing aneurodegenerative disease in a subject is performed by contacting thesample with one or more autoantigens that are specific for aneurodegenerative disease diagnostic autoantibody under conditions thatallow an immunocomplex of the autoantigen and the autoantibody to form,and detecting the presence of the immunocomplex, and is described indetail hereinabove. Autoantigens may provided in the form of an array,or preferably, a microarray.

Another embodiment of this invention includes a method of generating ansubject-specific, neurodegenerative disease specific autoantibodyprofile comprising obtaining an immunoglobulin-containing biologicalsample from a subject, performing an assay to determine the presence orabsence of one or more neurodegenerative disease diagnosticautoantibodies in the biological sample, and generating asubject-specific neurodegenerative disease diagnostic autoantibodyprofile of the disease diagnostic autoantibodies present in the sample.

In a more preferred embodiment, the neurodegenerative disease isselected from the group consisting of Alzheimer's disease, Parkinson'sdisease, amyotrophic lateral sclerosis, multiple sclerosis,Guillain-Barre syndrome, chronic peripheral neuropathy, optic neuritis,vascular dementia, obsessive compulsive disorder, Sydenham's chorea,PANDAS, Hashimoto's encephalopathy, schizophrenia, systemic lupuserythematosus, vascular cognitive disorders, stroke, Huntington'sdisease, neuromyelitis optica, paraneoplastic syndromes, limbicencephalitis, Rasmussen encephalitis, Hashimoto's encephalitis,encephalitis lethargica, stiff person syndrome, post-streptococcalmovement disorders, rheumatic fever, gluten enteropathy, ASD, dyslexia,HTLV-1-associated myelopathy/tropical spastic paraparesis, myastheniagravis, Lambert-Eaton syndrome, and arthrogryposis multiplex congenita.

In a preferred embodiment of the invention, the subject is a human.

In a preferred embodiment of the invention, theimmunoglobulin-containing biological sample is serum, whole blood, CSF,saliva, or sputum. A blood sample may be obtained by methods known inthe art including venipuncture or a finger stick. CSF may be obtained bymethods known in the art including a lumbar spinal tap. To obtain serumfrom blood, a sample of blood is received and centrifuged at a speedsufficient to pellet all cells and platelets, and the serum to beanalyzed is drawn from the resulting supernatant. Sputum and salivasamples may be collected by methods known in the art. The biologicalsamples may be diluted with a suitable buffer.

In a preferred embodiment, the assay used to diagnose aneurodegenerative disease in a subject is performed by contacting thesample with one or more autoantigens that are specific for aneurodegenerative disease-specific autoantibody under conditions thatallow an immunocomplex of the autoantigen and the antibody to form, anddetecting the presence of the immunocomplex, and is described in detailhereinabove. Autoantigens may be provided in the form of an array, orpreferably, a microarray.

Another embodiment of this invention provides a substrate on which oneor more autoantigens that are specific for a neurodegenerative diseasediagnostic autoantibody are immobilized. The present invention alsoprovides, in another embodiment, a microarray comprising a substrate onwhich one or more autoantigens that are specific for a neurodegenerativedisease diagnostic autoantibody are immobilized. The substrates andmicroarrays may be made as described hereinabove and are useful forcreating neurodegenerative disease diagnostic autoantibody profiles andfor the diagnosis of a neurodegenerative disease. An autoantigen maycomprise a protein antigen, or a polypeptide or peptide fragment thereofcontaining one or more epitopes recognized by the disease diagnosticautoantibody, or an epitope peptidomimetic that is recognized by thedisease diagnostic autoantibody. The substrates and microarrays containat least one autoantigen specific for each neurodegenerative disease,and preferably contain from about two to about thirty autoantigensspecific for each neurodegenerative disease.

The substrates and microarrays may contain a plurality of panels ofautoantigens wherein each panel contains autoantigens that arediagnostic for a particular neurodegenerative disease. Suchmulti-substrates and multi-arrays allow the diagnosis of more than oneneurodegenerative disease in the same assay, and also allow thedifferentiation of neurodegenerative diseases.

In a preferred embodiment, the neurodegenerative disease is selectedfrom the group consisting of Alzheimer's disease, Parkinson's disease,amyotrophic lateral sclerosis, multiple sclerosis, Guillain-Barresyndrome, chronic peripheral neuropathy, optic neuritis, vasculardementia, obsessive compulsive disorder, Sydenham's chorea, PANDAS,Hashimoto's encephalopathy, schizophrenia, systemic lupus erythematosus,vascular cognitive disorders, stroke, Huntington's disease,neuromyelitis optica, paraneoplastic syndromes, limbic encephalitis,Rasmussen encephalitis, Hashimoto's encephalitis, encephalitislethargica, stiff person syndrome, post-streptococcal movementdisorders, rheumatic fever, gluten enteropathy, ASD, dyslexia,HTLV-1-associated myelopathy/tropical spastic paraparesis, myastheniagravis, Lambert-Eaton syndrome, and arthrogryposis multiplex congenita.

In a further embodiment, the present invention provides a kit fordetecting neurodegenerative disease specific autoantibodies in a sample.The kit comprises one or more autoantigens that are specific for aneurodegenerative disease specific autoantibody and means fordetermining binding of the autoantigen to an autoantibody in the sample.The kit may also comprise packaging material comprising a label thatindicates that the one or more autoantigens of the kit can be used forthe identification of a neurodegenerative disease. Other components suchas buffers, controls, detection reagents, and the like known to those ofordinary skill in art may be included in such the kits. The kits areuseful for detecting neurodegenerative disease specific autoantibodiesand for diagnosing neurodegenerative diseases.

Alzheimer's Disease

Alzheimer's disease (AD)-diagnostic autoantibodies are defined herein asantibodies that specifically bind to protein or peptide antigens and arediagnostic indicators that can be used to differentiate Alzheimer'sDisease from control subjects without AD. Protein antigens that havebeen identified as being potentially useful diagnostic indicators areset forth in the following Table 1. The protein antigens in Table 1 areidentified by art-accepted names as well as database identificationnumbers. The database identification numbers refer to the publicallyavailable protein databases of the National Center for BiotechnologyInformation (NCBI), which are well-known and accessible to those ofordinary skill in the art.

TABLE 1 Database ID Description NM_024754.2 pentatricopeptide repeatdomain 2 (PTCD2) BC051695.1 FERM domain containing 8 (FRMD8) NM_014280.1DnaJ homolog subfamily C member 8 BC064984.1 additional sex combs like 1(Drosophila) (ASXL1) NM_003384.1 vaccinia related kinase 1 (VRK1)NM_001544.2 intercellular adhesion molecule 4 (Landsteiner-Wiener bloodgroup) (ICAM4), transcript variant 1 NM_001896.2 casein kinase 2, alphaprime polypeptide (CSNK2A2) NM_021104.1 ribosomal protein L41 (RPL41),transcript variant 1 BC016380.1 cDNA clone MGC: 27376 IMAGE: 4688477,complete cds NM_012387.1 peptidyl arginine deiminase, type IV (PADI4)NM_003135.1 Signal recognition particle 19 kDa protein BC022524.1fibroblast growth factor 12 (FGF12) BC000758.1 Coiled-coildomain-containing protein 28A NM_021032.2 fibroblast growth factor 12(FGF12), transcript variant 1 NM_022343.2 Golgi-associated plantpathogenesis-related protein 1 BC004236.2 ubiquitin-conjugating enzymeE2S (UBE2S) NM_000983.3 60S ribosomal protein L22 NM_017588.1 WD repeatdomain 5 (WDR5), transcript variant 1 NM_018956.2 chromosome 9 openreading frame 9 (C9orf9) BC033178.1 immunoglobulin heavy constant gamma3 (G3m marker) (IGHG3) NM_006628.4 cyclic AMP phosphoprotein, 19 kD(ARPP-19) BC022098.1 cDNA clone MGC: 31944 IMAGE: 4878869, complete cdsNM_001641.2 APEX nuclease (multifunctional DNA repair enzyme) 1 (APEX1),transcript variant 1 NM_003668.2 mitogen-activated proteinkinase-activated protein kinase 5 (MAPKAPK5), transcript variant 1NM_015933.1 coiled-coil domain containing 72 (CCDC72) PHC1244 chemokine(C-C motif) ligand 19 (CCL19) BC007782.2 immunoglobulin lambda constant1 (Mcg marker) (IGLC1) BC006423.1 Serine/threonine-protein kinase 6BC042628.1 serpin peptidase inhibitor, clade E (nexin, plasminogenactivator inhibitor type 1), member 2 (SERPINE2) BC021561.1 FACT complexsubunit SPT16 BC005248.1 eukaryotic translation initiation factor 1A,Y-linked (EIF1AY) NM_006223.1 protein (peptidylprolyl cis/transisomerase) NIMA-interacting, 4 (parvulin) (PIN4) NM_032377.2 elongationfactor 1 homolog (S. cerevisiae) (ELOF1) BC057774.1 RNA(guanine-9-)-methyltransferase domain-containing protein 3 NM_004196.2Cyclin-dependent kinase-like 1 BC001662.1 MAP kinase-activated proteinkinase 3 NM_015920.3 40S ribosomal protein S27-like protein NM_001031.440S ribosomal protein S28 NM_003688.1 Peripheral plasma membrane proteinCASK BC048970.1 tubulin tyrosine ligase-like family, member 7 (TTLL7)NM_000984.2 ribosomal protein L23a (RPL23A) NM_018439.1 Impact homolog(mouse) (IMPACT) NM_002305.2 lectin, galactoside-binding, soluble, 1(galectin 1) (LGALS1) BC056508.1 variable charge, Y-linked 1B (VCY)BC090938.1 Ig gamma-1 chain C region NM_002013.2 FK506 binding protein3, 25 kDa (FKBP3) NM_007278.1 GABA(A) receptor-associated protein(GABARAP) BC007228.1 CSAG family, member 3A (CSAG3A) BC033758.1centaurin, alpha 2 (CENTA2) BC092518.1 Ig gamma-1 chain C regionBC019598.1 Zinc finger matrin-type protein 4 NM_145909.1 Zinc fingerprotein 323 NM_003516.2 histone cluster 2, H2aa3 (HIST2H2AA3)NM_006838.1 methionyl aminopeptidase 2 (METAP2) BC026038.1 Ig gamma-1chain C region NM_002129.2 high-mobility group box 2 (HMGB2) NM_002677.1peripheral myelin protein 2 (PMP2) BC001132.1 DEAD (Asp-Glu-Ala-Asp) boxpolypeptide 54 (DDX54) NM_001001794.1 family with sequence similarity116, member B (FAM116B) NM_001997.2 Finkel-Biskis-Reilly murine sarcomavirus (FBR-MuSV) ubiquitously expressed (FAU) BC021174.1 Small EDRK-richfactor 1 NM_001028.2 ribosomal protein S25 (RPS25) NM_003512.3 HistoneH2A type 1-C NM_002095.1 general transcription factor IIE, polypeptide2, beta 34 kDa (GTF2E2) NM_005720.1 actin related protein 2/3 complex,subunit 1B, 41 kDa (ARPC1B) NM_003868.1 fibroblast growth factor 16(FGF16) NM_004214.3 fibroblast growth factor (acidic) intracellularbinding protein (FIBP), transcript variant 2 NM_021079.2N-myristoyltransferase 1 (NMT1) NM_015833.1 adenosine deaminase,RNA-specific, B1 (RED1 homolog rat) (ADARB1), transcript variant 2PHR5001 Recombinant human CTLA-4/Fc BC030983.1 immunoglobulin lambdalocus (IGL@) BC030984.1 cDNA clone MGC: 32654 IMAGE: 4701898, completecds NM_133494.1 NIMA (never in mitosis gene a)-related kinase 7 (NEK7)BC010467.1 cDNA clone MGC: 17410 IMAGE: 4156035, complete cdsNM_014060.1 malignant T cell amplified sequence 1 (MCTS1) NM_016167.3nucleolar protein 7, 27 kDa (NOL7) BC015833.1 cDNA clone MGC: 27152IMAGE: 4691630, complete cds NM_145063.1 chromosome 6 open reading frame130 (C6orf130) BC040106.1 hypothetical protein HSPC111 (HSPC111)BC010947.1 signal recognition particle 19 kDa (SRP19) NM_014065.2Protein asteroid homolog 1 BC012760.2 Glycogen synthase kinase-3 betaNM_004088.1 deoxynucleotidyltransferase, terminal (DNTT), transcriptvariant 1 BC019337.1 immunoglobulin heavy constant gamma 1 (G1m marker)(IGHG1) NM_002938.2 ring finger protein 4 (RNF4) NM_006620.2 HBS1-like(S. cerevisiae) (HBS1L) NM_000992.2 60S ribosomal protein L29NM_024668.2 ankyrin repeat and KH domain containing 1 (ANKHD1),transcript variant 3 NM_031445.1 AMME chromosomal region gene 1-like(AMMECR1L) NM_003517.2 histone cluster 2, H2ac (HIST2H2AC) BC072419.1 Iggamma-1 chain C region NM_145174.1 DnaJ (Hsp40) homolog, subfamily B,member 7 (DNAJB7) BC022361.1 rRNA-processing protein FCF1 homologBC006376.1 N-myristoyltransferase 2 (NMT2) NM_001895.1 casein kinase 2,alpha 1 polypeptide (CSNK2A1), transcript variant 2 NM_003524.2 HistoneH2B type 1-H BC027951.1 Cas scaffolding protein family member 4NM_134427.1 regulator of G-protein signaling 3 (RGS3), transcriptvariant 4 NM_052969.1 ribosomal protein L39-like (RPL39L) NM_023080.1chromosome 8 open reading frame 33 (C8orf33) NM_138779.1 chromosome 13open reading frame 27 (C13orf27) BC026030.1 zinc finger protein 239(ZNF239) BC029760.1 OTU domain containing 6B (OTUD6B) PHC1475 C-C motifchemokine 21 NM_133336.1 Wolf-Hirschhorn syndrome candidate 1 (WHSC1),transcript variant 9 BC034142.1 immunoglobulin kappa variable 1-5(IGKV1-5) NM_020235.2 bobby sox homolog (Drosophila) (BBX) NM_198829.1Ras-related C3 botulinum toxin substrate 1 BC098112.1 Histone H2B type1-N NM_032359.1 chromosome 3 open reading frame 26 (C3orf26) NM_001966.2Peroxisomal bifunctional enzyme BC032451.1 cDNA clone MGC: 40426 IMAGE:5178085, complete cds XM_379117.1 PREDICTED: Homo sapiens hypotheticalprotein LOC150568 (LOC150568) BC033159.1 DnaJ (Hsp40) homolog, subfamilyC, member 8 (DNAJC8) NM_006756.2 transcription elongation factor A(SII), 1 (TCEA1), transcript variant 1 NM_016940.1 RWD domain containing2B (RWDD2B) NM_177559.2 casein kinase 2, alpha 1 polypeptide (CSNK2A1),transcript variant 1 NM_004178.3 TAR (HIV-1) RNA binding protein 2(TARBP2), transcript variant 3 NM_032338.2 chromosome 12 open readingframe 31 (C12orf31) BC005955.1 chromosome 8 open reading frame 53(C8orf53) NM_001009613.1 Sperm protein associated with the nucleus onthe X chromosome N4 BC036723.1 Fc fragment of IgG, low affinity IIIa,receptor (CD16a) (FCGR3A) NM_003690.3 Interferon-inducible doublestranded RNA-dependent protein kinase activator A NM_014473.2 DIM1dimethyladenosine transferase 1-like (S. cerevisiae) (DIMT1L)NM_032855.1 hematopoietic SH2 domain containing (HSH2D) NM_001167.2baculoviral IAP repeat-containing 4 (BIRC4) NM_178571.2 hypotheticalprotein MGC51025 (MGC51025) NM_003600.1 aurora kinase A (AURKA),transcript variant 2 NM_006912.3 Ras-like without CAAX 1 (RIT1)NM_005307.1 G protein-coupled receptor kinase 4 BC001280.1Serine/threonine-protein kinase 6 NM_182970.2 regulating synapticmembrane exocytosis 4 (RIMS4) NM_153332.2 three prime histone mRNAexonuclease 1 (THEX1) NM_139016.2 chromosome 20 open reading frame 198(C20orf198) NM_003677.3 Density-regulated protein NM_013293.1Transformer-2 protein homolog BC033856.1 La ribonucleoprotein domainfamily, member 1 (LARP1) NM_000939.1 proopiomelanocortin(adrenocorticotropin/beta-lipotropin/ alpha-melanocyte stimulatinghormone/beta-melanocyte stimulating hormone/beta-endorphin) (POMC),transcript variant 2 BC009348.2 cirrhosis, autosomal recessive 1A(cirhin) (CIRH1A) NM_014508.2 apolipoprotein B mRNA editing enzyme,catalytic polypeptide- like 3C (APOBEC3C), mRNA. NM_080659.1 chromosome11 open reading frame 52 (C11orf52) NM_022755.2 inositol1,3,4,5,6-pentakisphosphate 2-kinase (IPPK) NM_002690.1 polymerase (DNAdirected), beta (POLB) BC011668.1 Casein kinase II subunit alphaNM_002128.2 high-mobility group box 1 (HMGB1) BC012472.1 ubiquitin D(UBD) BC030020.2 DEAD (Asp-Glu-Ala-Asp) box polypeptide 55 (DDX55)BC018060.1 Ras-like without CAAX 2 (RIT2) NM_003141.2 tripartitemotif-containing 21 (TRIM21) NM_007054.1 kinesin family member 3A(KIF3A) NM_006924.3 splicing factor, arginine/serine-rich 1 (splicingfactor 2, alternate splicing factor) (SFRS1), transcript variant 1NM_032563.1 late cornified envelope 3D (LCE3D) NM_173080.1 smallproline-rich protein 4 (SPRR4) NM_003527.4 Histone H2B type 1-OBC009762.2 Tripartite motif-containing protein 41 NM_006861.2 RAB35,member RAS oncogene family (RAB35) NM_002136.1 heterogeneous nuclearribonucleoprotein A1 (HNRNPA1), transcript variant 1 BC009623.1nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1)NM_021063.2 Histone H2B type 1-D BC054021.1 pterin-4 alpha-carbinolaminedehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha(TCF1) 2 (PCBD2) NM_012108.1 signal transducing adaptor family member 1(STAP1) NM_023937.1 mitochondrial ribosomal protein L34 (MRPL34),nuclear gene encoding mitochondrial protein XM_088679.2 Spermatidnuclear transition protein 4 NM_022720.5 DiGeorge syndrome criticalregion gene 8 (DGCR8) NM_016073.2 hepatoma-derived growth factor,related protein 3 (HDGFRP3) NM_018105.1 THAP domain containing,apoptosis associated protein 1 (THAP1), transcript variant 1 NM_005371.2methyltransferase like 1 (METTL1), transcript variant 1 BC029427.1coiled-coil domain containing 23 (CCDC23) NM_032476.1 mitochondrialribosomal protein S6 (MRPS6), nuclear gene encoding mitochondrialprotein NM_003089.4 small nuclear ribonucleoprotein 70 kDa polypeptide(RNP antigen) (SNRP70) BC020972.1 Casein kinase I isoform gamma-2BC000381.2 TBP-like 1 (TBPL1) NM_007285.5 GABA(A) receptor-associatedprotein-like 2 (GABARAPL2) NM_004060.2 cyclin G1 (CCNG1), transcriptvariant 1 BC001780.1 Uncharacterized methyltransferase WBSCR22NM_022048.1 casein kinase 1, gamma 1 (CSNK1G1) BC035256.1 Putativeadenylate kinase 7 NM_175887.2 proline rich 15 (PRR15) BC010919.1ribosomal protein L35 (RPL35) NM_016207.2 cleavage and polyadenylationspecific factor 3, 73 kDa (CPSF3) BC000784.1 baculoviral IAPrepeat-containing 5 (survivin) (BIRC5) NM_002364.1 melanoma antigenfamily B, 2 (MAGEB2) NM_022839.2 mitochondrial ribosomal protein S11(MRPS11), nuclear gene encoding mitochondrial protein, transcriptvariant 1 NM_014370.2 SFRS protein kinase 3 (SRPK3) NM_016505.2 zincfinger, CCHC domain containing 17 (ZCCHC17) BC030813.1 cDNA clone MGC:22645 IMAGE: 4700961, complete cds BC020803.1 developmentally regulatedGTP binding protein 1 (DRG1) NM_205848.1 synaptotagmin VI (SYT6)NM_006398.2 Ubiquitin D NM_017646.3 tRNA isopentenyltransferase 1(TRIT1) NM_006925.2 Splicing factor, arginine/serine-rich 5 NM_153822.1proteasome (prosome, macropain) 26S subunit, non-ATPase, 4 (PSMD4),transcript variant 2 NM_014321.2 origin recognition complex, subunit 6like (yeast) (ORC6L) BC012876.1 Ig lambda chain C regions NM_021967.1small EDRK-rich factor 1A (telomeric) (SERF1A) NM_003295.1 tumorprotein, translationally-controlled 1 (TPT1) NM_017503.2 surfeit 2(SURF2) BC018137.1 TATA box binding protein (TBP)-associated factor, RNApolymerase I, B, 63 kDa (TAF1B) BC005004.1 family with sequencesimilarity 64, member A (FAM64A) NM_152373.2 zinc finger protein 684(ZNF684) NM_000989.2 ribosomal protein L30 (RPL30) NM_000800.2fibroblast growth factor 1 (acidic) (FGF1), transcript variant 1NM_000975.2 ribosomal protein L11 (RPL11) PHC1695 C—X—C motif chemokine11 NM_022140.2 Band 4.1-like protein 4A NM_016287.2 heterochromatinprotein 1, binding protein 3 (HP1BP3) BC015586.2 laminin, gamma 1(formerly LAMB2) (LAMC1) NM_023931.1 zinc finger protein 747 (ZNF747)NM_153207.2 AE binding protein 2 (AEBP2) NM_007079.2 Protein tyrosinephosphatase type IVA 3 NM_004397.3 Probable ATP-dependent RNA helicaseDDX6 NM_012424.2 Ribosomal protein S6 kinase delta-1 NM_020239.2 CDC42small effector 1 (CDC42SE1), transcript variant 2 BC029378.1 telomericrepeat binding factor (NIMA-interacting) 1 (TERF1) BC000306.1hydroxyacyl-Coenzyme A dehydrogenase (HADH) NM_182692.1Serine/threonine-protein kinase SRPK2 NM_032350.3 Uncharacterizedprotein C7orf50 NM_001022.3 ribosomal protein S19 (RPS19) NM_001002913.1peptidyl-tRNA hydrolase 1 homolog (S. cerevisiae) (PTRH1) BC000535.1Suppressor of SWI4 1 homolog NM_017692.1 aprataxin (APTX), transcriptvariant 4 NM_000993.2 ribosomal protein L31 (RPL31), transcript variant1 NM_152653.1 ubiquitin-conjugating enzyme E2E 2 (UBC4/5 homolog, yeast)(UBE2E2) NM_014891.1 PDGFA associated protein 1 (PDAP1) NM_012148.1double homeobox, 3 (DUX3) NM_024046.1 CaM kinase-like vesicle-associated(CAMKV) NM_022063.1 chromosome 10 open reading frame 84 (C10orf84)BC036434.1 Serine/threonine-protein kinase VRK2 NM_001396.2 Dualspecificity tyrosine-phosphorylation-regulated kinase 1A NM_004939.1DEAD (Asp-Glu-Ala-Asp) box polypeptide 1 (DDX1) NM_001039724.1 NostrinNM_138551.1 thymic stromal lymphopoietin (TSLP), transcript variant 2XM_379194.1 PREDICTED: Homo sapiens hypothetical LOC401068 (LOC401068)BC007401.2 cell division cycle 25 homolog A (S. pombe) (CDC25A)BC008902.2 GRIP and coiled-coil domain-containing protein 1 BC019039.2Regulator of G-protein signaling 3 NM_016050.1 mitochondrial ribosomalprotein L11 (MRPL11), nuclear gene encoding mitochondrial protein,transcript variant 1 NM_002927.3 regulator of G-protein signaling 13(RGS13), transcript variant 1 NM_207430.1 FLJ46266 protein (FLJ46266),mRNA. NM_016508.2 Cyclin-dependent kinase-like 3 NM_197964.1 chromosome7 open reading frame 55 (C7orf55) BC021930.1 KIAA1530 protein (KIAA1530)NM_145043.1 nei like 2 (E. coli) (NEIL2) BC030586.2 signal transducingadaptor molecule (SH3 domain and ITAM motif) 1 (STAM) BC004292.1 PHDfinger protein 15 (PHF15) BC022378.1 zinc finger with KRAB and SCANdomains 1 (ZKSCAN1) NM_003792.1 endothelial differentiation-relatedfactor 1 (EDF1), transcript variant alpha BC070154.1 Non-histonechromosomal protein HMG-14 BC010074.2 FUS interacting protein(serine/arginine-rich) 1 (FUSIP1) NM_002201.3 interferon stimulatedexonuclease gene 20 kDa (ISG20) BC033621.2 Pseudouridylate synthase 7homolog-like protein NM_004114.2 fibroblast growth factor 13 (FGF13),transcript variant 1A NM_012420.1 interferon-induced protein withtetratricopeptide repeats 5 (IFIT5) NM_016203.2 protein kinase,AMP-activated, gamma 2 non-catalytic subunit (PRKAG2), transcriptvariant a, mRNA. NM_014878.2 Pumilio domain-containing protein KIAA0020NM_018664.1 Jun dimerization protein p21SNFT (SNFT) NM_002402.1 mesodermspecific transcript homolog (mouse) (MEST), transcript variant 1NM_003769.2 splicing factor, arginine/serine-rich 9 (SFRS9) NM_018132.3centromere protein Q (CENPQ) NM_006072.4 chemokine (C-C motif) ligand 26(CCL26) NM_021029.3 ribosomal protein L36a (RPL36A) NM_000978.2ribosomal protein L23 (RPL23) NM_001023.2 ribosomal protein S20 (RPS20)BC013366.2 UNC-112 related protein 2 (URP2) BC001327.1interferon-related developmental regulator 2 (IFRD2) BC000522.1 serpinpeptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epitheliumderived factor), member 1 (SERPINF1) NM_019067.1 guanine nucleotidebinding protein-like 3 (nucleolar)-like (GNL3L) NM_152634.1 TFS2-Mdomain-containing protein 1 (MGC17403) BC011842.2 hypothetical proteinFLJ11184 (FLJ11184) BC068514.1 NF-kappaB repressing factor (NKRF)NM_018063.3 helicase, lymphoid-specific (HELLS) NM_198467.1 roundspermatid basic protein 1-like (RSBN1L) NM_198517.2 TBC1 domain family,member 10C (TBC1D10C) NM_001564.1 inhibitor of growth family, member 2(ING2) NM_002930.1 GTP-binding protein Rit2 NM_019058.1DNA-damage-inducible transcript 4 protein NM_020661.1 activation-inducedcytidine deaminase (AICDA) NM_173822.1 family with sequence similarity126, member B (FAM126B) BC056887.1 chromosome 5 open reading frame 5(C5orf5) BC070334.1 immunoglobulin kappa constant (IGKC) NM_004071.1Dual specificity protein kinase CLK1 NM_005801.2 eukaryotic translationinitiation factor 1 (EIF1) BC001487.2 TAR DNA-binding protein 43NM_006790.1 myotilin (MYOT) NM_175923.2 hypothetical protein MGC42630(MGC42630) NM_000122.1 excision repair cross-complementing rodent repairdeficiency, complementation group 3 (xeroderma pigmentosum group Bcomplementing) (ERCC3) BC010501.1 Catenin delta-1 BC005298.1cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activatingkinase) (CDK7) PHC0076 interleukin 7 (IL7) NM_138349.2 Tumor proteinp53-inducible protein 13 BC000044.1 Spindlin-2B NM_014747.2 regulatingsynaptic membrane exocytosis 3 (RIMS3) NM_001014.2 ribosomal protein S10(RPS10) NM_005678.3 SNRPN upstream reading frame (SNURF), transcriptvariant 1 BC010876.1 nei endonuclease VIII-like 1 (E. coli) (NEIL1)BC025281.1 RNA binding motif protein 9 (RBM9) NM_001013.2 ribosomalprotein S9 (RPS9) NM_015414.2 ribosomal protein L36 (RPL36), transcriptvariant 2 NM_017566.2 kelch domain containing 4 (KLHDC4) BC015818.1lectin, galactoside-binding, soluble, 8 (galectin 8) (LGALS8) BC036109.1SECIS binding protein 2 (SECISBP2) NM_005738.1 ADP-ribosylationfactor-like 4A (ARL4A), transcript variant 1 BC022816.1 NA NM_024303.1zinc finger and SCAN domain containing 5 (ZSCAN5) BC018823.2 splicingfactor, arginine/serine-rich 5 (SFRS5) NM_024319.1 chromosome 1 openreading frame 35 (C1orf35) PV3359 Ephrin receptor A3 (EPHA3), transcriptvariant 1 NM_145899.1 high mobility group AT-hook 1 (HMGA1), transcriptvariant 1 NM_021158.1 tribbles homolog 3 (Drosophila) (TRIB3)NM_005794.2 dehydrogenase/reductase (SDR family) member 2 (DHRS2),transcript variant 2 BC005807.2 stearoyl-CoA desaturase(delta-9-desaturase) (SCD) NM_006374.2 serine/threonine kinase 25 (STE20homolog, yeast) (STK25) NM_152757.1 Putative uncharacterized proteinC20orf200 NM_001009880.1 chromosome 22 open reading frame 9 (C22orf9),transcript variant 2 NM_138558.1 protein phosphatase 1, regulatory(inhibitor) subunit 8 (PPP1R8), transcript variant 2 BC007852.1Serine/threonine-protein kinase 25 NM_012396.1 pleckstrin homology-likedomain, family A, member 3 (PHLDA3) NM_012437.2 SNAP-associated protein(SNAPAP) PHC0205 interleukin 20 (IL20) NM_016093.2 ribosomal proteinL26-like 1 (RPL26L1) NM_005902.1 SMAD family member 3 (SMAD3)XM_375456.2 Ataxin-7-like protein 3 NM_006275.2 splicing factor,arginine/serine-rich 6 (SFRS6) BC011600.1 cDNA clone IMAGE: 3050953,**** WARNING: chimeric clone **** NM_014570.2 ADP-ribosylation factorGTPase activating protein 3 (ARFGAP3) NM_022551.2 ribosomal protein S18(RPS18) BC063275.1 eukaryotic translation initiation factor 2C, 1(EIF2C1) BC062423.1 chromosome 7 open reading frame 41 (C7orf41)BC096708.1 Wilms tumor-associated protein NM_199123.1 SET domaincontaining 3 (SETD3), transcript variant 2 BC010907.1 PAK1 interactingprotein 1 (PAK1IP1) NM_004217.1 aurora kinase B (AURKB) NM_005737.3ADP-ribosylation factor-like 4C (ARL4C) NM_020467.2 small trans-membraneand glycosylated protein (LOC57228), transcript variant 2 BC021180.2high-mobility group box 4 (HMGB4) NM_004728.2 DEAD (Asp-Glu-Ala-Asp) boxpolypeptide 21 (DDX21) BC030702.1 microcephaly, primary autosomalrecessive 1 (MCPH1) NM_003724.1 jerky homolog (mouse) (JRK), transcriptvariant 1 NM_016077.1 peptidyl-tRNA hydrolase 2 (PTRH2), nuclear geneencoding mitochondrial protein NM_014955.2 KIAA0859 (KIAA0859),transcript variant 2 NM_003503.2 Cell division cycle 7-related proteinkinase BC017212.2 PHD finger protein 11 (PHF11) NM_019069.3 WD repeatdomain 5B (WDR5B) BC094719.1 Rho GTPase-activating protein 12 BC021187.1DKFZP434K028 protein (DKFZP434K028) NM_003948.2 Cyclin-dependentkinase-like 2 BC040183.2 Rap guanine nucleotide exchange factor (GEF) 4(RAPGEF4) NM_014061.3 melanoma antigen family H, 1 (MAGEH1) BC032587.1tubby like protein 3 (TULP3) BC005332.1 cDNA clone MGC: 12418 IMAGE:3934658, complete cds BC033710.2 RAD54 homolog B (S. cerevisiae)(RAD54B) BC010425.1 acyl-Coenzyme A oxidase 1, palmitoyl (ACOX1)NM_021138.2 TNF receptor-associated factor 2 (TRAF2) BC093990.1 Sin3histone deacetylase corepressor complex component SDS3 NM_014288.2Centromere protein R NM_024826.1 Microtubule-associated protein 9BC035968.1 chloride intracellular channel 5 (CLIC5) BC096165.1 TroponinI, cardiac muscle BC012105.1 nuclear VCP-like (NVL) BC011924.1 unkempthomolog (Drosophila)-like (UNKL) NM_001311.2 Cysteine-rich protein 1NM_014445.2 stress-associated endoplasmic reticulum protein 1 (SERP1)NM_005979.1 S100 calcium binding protein A13 (S100A13), transcriptvariant 2 BC036923.1 chromosome 9 open reading frame 150 (C9orf150)NM_033671.1 cyclin B3 (CCNB3), transcript variant 2 BC014441.1NOL1/NOP2/Sun domain family, member 4 (NSUN4) BC031549.1 CDC-like kinase1 (CLK1) NM_194290.1 cDNA FLJ42001 fis, clone SPLEN2029912 (LOC153684protein) [Source: UniProtKB/TrEMBL; Acc: Q6ZVW3] BC053984.1immunoglobulin heavy variable 4-31 (IGHV4-31) BC050563.1 hypotheticalprotein LOC202051 (LOC202051) BC050718.1 polymerase (DNA directed) kappa(POLK) BC000896.1 RAB10, member RAS oncogene family (RAB10) NM_006252.2AMP-activated protein_kinase A2/B1/G1: PRKAA2/B1/G1 sequences areseperated by -- (in protein list file). BC013630.1 JTV1 gene (JTV1)BC009108.1 cDNA clone IMAGE: 3451214 (MCM10) BC002645.1 syntaxin 5(STX5) NM_138414.1 coiled-coil domain containing 101 (CCDC101)NM_002740.1 protein kinase C, iota (PRKCI) NM_002822.3 twinfilin,actin-binding protein, homolog 1 (Drosophila) (TWF1) BC003566.1 zincfinger protein 24 (ZNF24) NM_022756.2 Uncharacterized protein C1orf149NM_153035.1 chromosome 1 open reading frame 83 (C1orf83) NM_177524.1mesoderm specific transcript homolog (mouse) (MEST), transcript variant2 NM_004635.2 mitogen-activated protein kinase-activated protein kinase3 (MAPKAPK3) NM_005607.1 Focal adhesion kinase 1 BC010697.1 RNA-bindingprotein 40 NM_174942.1 GAS2-like protein 3 BC038976.1 RhoGTPase-activating protein 15 NM_012117.1 chromobox homolog 5 (HP1 alphahomolog, Drosophila) (CBX5) NM_013313.3 yippee-like 1 (Drosophila)(YPEL1) NM_148179.1 chromosome 9 open reading frame 23 (C9orf23),transcript variant 2 BC038105.2 membrane protein, palmitoylated 7 (MAGUKp55 subfamily member 7) (MPP7) BC091489.1 zinc finger, MYND domaincontaining 11, mRNA (cDNA clone MGC: 111056 IMAGE: 6186814), completecds BC034435.1 zinc finger CCCH-type containing 3 (ZC3H3) NM_152736.2Zinc finger protein 187 NM_015014.1 RNA binding motif protein 34 (RBM34)NM_003137.2 SFRS protein kinase 1 (SRPK1) BC016486.1 lectin,galactoside-binding, soluble, 8 (galectin 8) (LGALS8) BC000238.1 ankyrinrepeat and zinc finger domain containing 1 (ANKZF1) NM_002904.4 RD RNAbinding protein (RDBP) BC009046.1 neurogenic differentiation 1 (NEUROD1)NM_198965.1 Parathyroid hormone-related protein BC047776.2 coiled-coildomain containing 43 (CCDC43) NM_001004306.1 similar to hypotheticalprotein FLJ36492 (MGC87631) NM_006800.2 male-specific lethal 3-like 1(Drosophila) (MSL3L1), transcript variant 3 NM_006038.1 spermatogenesisassociated 2 (SPATA2) NM_014477.2 chromosome 20 open reading frame 10(C20orf10) BC027612.2 EP300-interacting inhibitor of differentiation 3NM_017411.2 survival of motor neuron 2, centromeric (SMN2), transcriptvariant d BC004876.1 Protein MCM10 homolog NM_201516.1 H2A histonefamily, member V (H2AFV), transcript variant 4 NM_022156.3dihydrouridine synthase 1-like (S. cerevisiae) (DUS1L) BC015742.1polymerase (DNA directed), eta (POLH) NM_001015509.1 Peptidyl-tRNAhydrolase 2, mitochondrial NM_014366.1 guanine nucleotide bindingprotein-like 3 (nucleolar) (GNL3), transcript variant 1 NM_018357.2 Laribonucleoprotein domain family, member 6 (LARP6), transcript variant 1BC020221.1 SH3 and cysteine rich domain (STAC) NM_005307.1 Gprotein-coupled receptor kinase 4 NM_017785.2 coiled-coil domaincontaining 99 (CCDC99) BC026101.2 nudE nuclear distribution gene Ehomolog (A. nidulans)-like 1 (NDEL1) NM_175571.2 GTPase, IMAP familymember 8 (GIMAP8) NM_004286.2 GTP binding protein 1 (GTPBP1) BC072461.1Cysteine and histidine-rich domain-containing protein 1 BC047945.1tripartite motif-containing 69 (TRIM69) BC005858.1 fibronectin 1 (FN1)NM_001722.2 polymerase (RNA) III (DNA directed) polypeptide D, 44 kDa(POLR3D) NM_024333.1 Fibronectin type III and SPRY domain-containingprotein 1 NM_144595.1 SLAIN motif family, member 1 (SLAIN1), transcriptvariant 2 NM_002469.1 myogenic factor 6 (herculin) (MYF6) BC053866.1endothelin 3 (EDN3) NM_001319.5 casein kinase 1, gamma 2 (CSNK1G2)BC006124.1 IMP (inosine monophosphate) dehydrogenase 2 (IMPDH2)NM_014667.1 vestigial like 4 (Drosophila) (VGLL4) NM_031465.2 chromosome12 open reading frame 32 (C12orf32) NM_182612.1 Parkinson disease 7domain containing 1 (PDDC1) PV4803 epidermal growth factor receptor(erythroblastic leukemia viral (verb-b) oncogene homolog, avian) (EGFR);see catalog number for detailed information on wild-type or point mutantstatus NM_152266.1 chromosome 19 open reading frame 40 (C19orf40)NM_000997.2 ribosomal protein L37 (RPL37) BC001728.1 TCF3 fusion partnerBC007015.1 cyclin E2 (CCNE2) NM_022347.1 interferon responsive gene 15(IFRG15) BC031821.1 Secernin-3 NM_016304.2 chromosome 15 open readingframe 15 (C15orf15) BC069677.1 Regulator of G-protein signaling 8BC013331.1 H2A histone family, member Y (H2AFY) NM_017838.2 nucleolarprotein family A, member 2 (H/ACA small nucleolar RNPs) (NOLA2),transcript variant 1 BC013796.1 adaptor-related protein complex 2, mu 1subunit (AP2M1) NM_080743.2 serine-arginine repressor protein (35 kDa)(SRrp35) BC000190.1 zinc finger, C3HC-type containing 1 (ZC3HC1)BC036089.1 myeloid/lymphoid or mixed-lineage leukemia (trithoraxhomolog, Drosophila); translocated to, 3 (MLLT3) NM_018215.2hypothetical protein FLJ10781 (FLJ10781), transcript variant 1BC095401.1 AKT-interacting protein NM_001008572.1 tubulin tyrosineligase-like family, member 1 (TTLL1), transcript variant 2 BC103812.1Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 BC036365.1 PHdomain-containing protein C10orf81 NM_016047.1 splicing factor 3B, 14kDa subunit (SF3B14) BC014949.1 DEXH (Asp-Glu-X-His) box polypeptide 58(DHX58) BC047690.1 Ras-related protein M-Ras NM_001894.2 casein kinase1, epsilon (CSNK1E), transcript variant 2 NM_006482.1 Dual specificitytyrosine-phosphorylation-regulated kinase 2 NM_025104.2 Protein DBF4homolog B NM_017819.1 RNA (guanine-9-)-methyltransferasedomain-containing protein 1, mitochondrial NM_199139.1 XIAP associatedfactor-1 (XAF1), transcript variant 2 NM_003910.2 BUD31 homolog (S.cerevisiae) (BUD31) BC000442.1 Serine/threonine-protein kinase 12BC028711.2 cancer/testis antigen CT45-3 (CT45-3) NM_018158.1 solutecarrier family 4 (anion exchanger), member 1, adaptor protein (SLC4A1AP)BC034692.1 anillin, actin binding protein (ANLN) NM_173605.1 potassiumchannel regulator (KCNRG), transcript variant 1 NM_014047.1 chromosome19 open reading frame 53 (C19orf53) BC073791.1 immunoglobulin kappaconstant, mRNA (cDNA clone MGC: 88809 IMAGE: 6279986), complete cdsBC014928.1 MYC-induced nuclear antigen BC053656.1 EGF-like repeats anddiscoidin I-like domains 3 (EDIL3) XM_378879.2 PREDICTED: Homo sapienshypothetical LOC400763 (LOC400763) NM_017817.1 RAB20, member RASoncogene family (RAB20) BC031608.1 REST corepressor 3 (RCOR3) BC047722.1hypothetical protein MGC52110 (MGC52110) BC020726.1 sciellin (SCEL)NM_024039.1 MIS12, MIND kinetochore complex component, homolog (yeast)(MIS12) BC026213.1 F-box/WD repeat-containing protein 11 NM_002135.3nuclear receptor subfamily 4, group A, member 1 (NR4A1), transcriptvariant 1 NM_015939.2 tRNA methyltransferase 6 homolog (S. cerevisiae)(TRMT6) NM_018039.2 jumonji domain containing 2D (JMJD2D) NM_007373.2soc-2 suppressor of clear homolog (C. elegans) (SHOC2) BC067120.1protein tyrosine phosphatase domain containing 1, mRNA (cDNA clone MGC:70358 IMAGE: 5539182), complete cds NM_015918.2 processing of precursor5, ribonuclease P/MRP subunit (S. cerevisiae) (POP5), transcript variant1 NM_152677.1 zinc finger and SCAN domain containing 4 (ZSCAN4)BC008902.2 GRIP and coiled-coil domain-containing protein 1NM_001008239.1 chromosome 18 open reading frame 25 (C18orf25),transcript variant 2 NM_183397.1 peroxisomal membrane protein 4, 24 kDa(PXMP4), transcript variant 2 NM_006337.3 microspherule protein 1(MCRS1), transcript variant 1 BC034401.1 cDNA clone IMAGE: 5172086,partial cds NM_006755.1 transaldolase 1 (TALDO1) NM_004853.1 syntaxin 8(STX8) BC036910.1 hypothetical LOC388882 (LOC388882) BC094687.1Elongation factor 1-alpha 1 NM_144608.1 hexamthylene bis-acetamideinducible 2 (HEXIM2) NM_003831.1 RIO kinase 3 (yeast) (RIOK3) BC009250.1guanine nucleotide binding protein-like 2 (nucleolar) (GNL2) BC032598.1NHL repeat containing 2 (NHLRC2) NM_018697.3 LanC lantibiotic synthetasecomponent C-like 2 (bacterial) (LANCL2) NM_024104.1 chromosome 19 openreading frame 42 (C19orf42) BC030665.1 Sulfotransferase 4A1 BC004955.1ATPase inhibitory factor 1 (ATPIF1) BC009010.1 Uncharacterized proteinC6orf142 homolog BC012887.1 Nucleolar and spindle-associated protein 1BC015066.1 core-binding factor, runt domain, alpha subunit 2;translocated to, 2 (CBFA2T2) BC052303.1 Rho GTPase activating protein 4(ARHGAP4) NM_080414.1 vacuolar protein sorting 16 homolog (S.cerevisiae) (VPS16), transcript variant 2 NM_001790.2 cell divisioncycle 25 homolog C (S. pombe) (CDC25C), transcript variant 1 PHC0045interleukin 4 (IL4), transcript variant 1 NM_145041.1 transmembraneprotein 106A (TMEM106A) NM_021639.2 GC-rich promoter binding protein1-like 1 (GPBP1L1) BC028295.1 peptidase D (PEPD) PV3612 aurora kinase A(AURKA), transcript variant 2 NM_032321.1 hypothetical protein MGC13057(MGC13057), transcript variant 4 BC010033.1 quinolinatephosphoribosyltransferase (nicotinate-nucleotide pyrophosphorylase(carboxylating)) (QPRT) NM_001064.1 Transketolase NM_017572.2 MAPkinase-interacting serine/threonine-protein kinase 2 NM_022650.1 RAS p21protein activator (GTPase activating protein) 1 (RASA1), transcriptvariant 2 NM_020781.2 zinc finger protein 398 (ZNF398), transcriptvariant 2 NM_002391.1 midkine (neurite growth-promoting factor 2) (MDK),transcript variant 3 NM_006298.2 zinc finger protein 192 (ZNF192)BC047536.1 sciellin (SCEL) NM_139062.1 casein kinase 1, delta (CSNK1D),transcript variant 2 NM_005639.1 synaptotagmin I (SYT1) BC006811.1peroxisome proliferator-activated receptor gamma (PPARG) BC008364.1heterogeneous nuclear ribonucleoprotein C (C1/C2) (HNRPC) NM_032345.1within bgcn homolog (Drosophila) (WIBG) BC016825.1 spire homolog 1(Drosophila) (SPIRE1) NM_020664.3 2,4-dienoyl CoA reductase 2,peroxisomal (DECR2) NM_017542.3 pogo transposable element with KRABdomain (POGK) NM_003160.1 Serine/threonine-protein kinase 13 BC026346.1family with sequence similarity 84, member A (FAM84A) BC041037.1immunoglobulin heavy constant mu (IGHM) BC033677.1 Uncharacterizedprotein C9orf114 BC055427.1 TRAF2 and NCK interacting kinase (TNIK)NM_016648.1 La ribonucleoprotein domain family, member 7 (LARP7),transcript variant 1 BC064145.1 CDK5 regulatory subunit associatedprotein 1-like 1 (CDKAL1) NM_138565.1 cortactin (CTTN), transcriptvariant 2 NM_022823.1 fibronectin type III domain containing 4 (FNDC4)BC006104.1 RIO kinase 1 (yeast) (RIOK1) BC014975.1 family with sequencesimilarity 136, member A (FAM136A) NM_138730.1 high mobility groupnucleosomal binding domain 3 (HMGN3), transcript variant 2 NM_025004.1Coiled-coil domain-containing protein 15 NM_004092.2 Enoyl-CoAhydratase, mitochondrial NM_021107.1 mitochondrial ribosomal protein S12(MRPS12), nuclear gene encoding mitochondrial protein, transcriptvariant 1 NM_053049.2 Urocortin-3 NM_001545.1 immature colon carcinomatranscript 1 (ICT1) NM_148571.1 mitochondrial ribosomal protein L27(MRPL27), nuclear gene encoding mitochondrial protein, transcriptvariant 2 NM_001003799.1 TCR gamma alternate reading frame protein(TARP), nuclear gene encoding mitochondrial protein, transcript variant1 BC017227.1 phosducin-like (PDCL) NM_172159.2 potassium voltage-gatedchannel, shaker-related subfamily, beta member 1 (KCNAB1), transcriptvariant 3 NM_000462.2 ubiquitin protein ligase E3A (human papillomavirus E6-associated protein, Angelman syndrome) (UBE3A), transcriptvariant 2 XM_210860.4 PREDICTED: Homo sapiens hypothetical LOC283034(LOC283034) BC022344.1 twinfilin, actin-binding protein, homolog 1(Drosophila) (TWF1) NM_005037.3 peroxisome proliferator-activatedreceptor gamma (PPARG), transcript variant 4 NM_022977.1 acyl-CoAsynthetase long-chain family member 4 (ACSL4), transcript variant 2NM_006217.2 serpin peptidase inhibitor, clade I (pancpin), member 2(SERPINI2) NM_024979.2 Guanine nucleotide exchange factor DBSNM_016286.1 dicarbonyl/L-xylulose reductase (DCXR) NM_003160.1Serine/threonine-protein kinase 13 NM_015687.2 filamin A interactingprotein 1 (FILIP1) BC005871.2 chromosome 10 open reading frame 58(C10orf58) NM_016216.2 Lariat debranching enzyme NM_017856.1 gem(nuclear organelle) associated protein 8 (GEMIN8), transcript variant 3NM_015869.2 peroxisome proliferator-activated receptor gamma (PPARG),transcript variant 2 NM_001003397.1 Tumor protein D53 NM_001018061.1UPF0544 protein C5orf45 [Source: UniProtKB/Swiss- Prot; Acc: Q6NTE8]BC013900.1 chromosome 12 open reading frame 41 (C12orf41) BC022988.1chromosome 6 open reading frame 65 (C6orf65) NM_006299.2 zinc fingerprotein 193 (ZNF193) BC018847.1 Transaldolase NM_139355.1megakaryocyte-associated tyrosine kinase (MATK), transcript variant 1NM_207356.1 chromosome 1 open reading frame 174 (C1orf174)NM_001008737.1 hypothetical LOC401052 (LOC401052) NM_145109.1mitogen-activated protein kinase kinase 3 (MAP2K3), transcript variant BBC017114.1 oligonucleotide/oligosaccharide-binding fold containing 2A(OBFC2A) XM_086879.4 PREDICTED: Homo sapiens hypothetical LOC150371(LOC150371) NM_078630.1 male-specific lethal 3-like 1 (Drosophila)(MSL3L1), transcript variant 2 NM_005197.2 Forkhead box protein N3NM_004602.2 Double-stranded RNA-binding protein Staufen homolog 1BC017504.1 Differentially expressed in FDCP 6 homolog NM_003590.2 cullin3 (CUL3) NM_145702.1 tigger transposable element derived 1 (TIGD1)BC001935.1 cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A)NM_004965.3 high-mobility group nucleosome binding domain 1 (HMGN1)BC032508.1 PNMA-like 1, mRNA (cDNA clone MGC: 45422 IMAGE: 5246377),complete cds BC013966.2 family with sequence similarity 64, member A(FAM64A) NM_020236.2 mitochondrial ribosomal protein L (MRPL1), nucleargene encoding mitochondrial protein BC043247.2 transducin-like enhancerof split 3 (E(sp1) homolog, Drosophila) (TLE3) BC057806.1 insulin-likegrowth factor binding protein 1 (IGFBP1) NM_006573.2 tumor necrosisfactor (ligand) superfamily, member 13b (TNFSF13B) BC025406.1phosphodiesterase 4D interacting protein (myomegalin) (PDE4DIP)BC002559.1 YTH domain family, member 2 (YTHDF2) NM_052926.1Paraneoplastic antigen-like protein 5 NM_006254.3 protein kinase C,delta (PRKCD), transcript variant 1 BC022003.1 myotubularin relatedprotein 9 (MTMR9) BC043348.2 retinitis pigmentosa 2 (X-linked recessive)(RP2) NM_018010.2 intraflagellar transport 57 homolog (Chlamydomonas)(IFT57) BC044851.1 vacuolar protein sorting 41 homolog (S. cerevisiae)(VPS41) BC068094.1 SH3 domain and tetratricopeptide repeats 1 (SH3TC1)NM_020961.2 KIAA1627 protein (KIAA1627) PV3757 myosin light chain kinase2, skeletal muscle (MYLK2) NM_002451.3 methylthioadenosine phosphorylase(MTAP), mRNA. NM_000281.1 pterin-4 alpha-carbinolaminedehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha(TCF1) (PCBD1) NM_144982.1 coiled-coil domain containing 131 (CCDC131)NM_017927.2 mitofusin 1 (MFN1), nuclear gene encoding mitochondrialprotein, transcript variant 2 NM_002150.1 4-hydroxyphenylpyruvatedioxygenase NM_016267.1 vestigial like 1 (Drosophila) (VGLL1) BC067299.1Mdm4, transformed 3T3 cell double minute 4, p53 binding protein (mouse)(MDM4) XM_378988.2 PREDICTED: Homo sapiens hypothetical LOC400849(LOC400849) NM_006466.1 polymerase (RNA) III (DNA directed) polypeptideF, 39 kDa (POLR3F) BC042608.1 family with sequence similarity 90, memberA1 (FAM90A1) NM_025136.1 optic atrophy 3 (autosomal recessive, withchorea and spastic paraplegia) (OPA3), transcript variant 2 BC012620.1golgi SNAP receptor complex member 1 (GOSR1) NM_139244.2 syntaxinbinding protein 5 (tomosyn) (STXBP5) NM_015929.2 lipoyltransferase 1(LIPT1), transcript variant 1 PV3366 v-erb-b2 erythroblastic leukemiaviral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog(avian) (ERBB2), transcript variant 2 NM_133629.1 RAD51-like 3 (S.cerevisiae) (RAD51L3), transcript variant 4 XM_294794.1 PREDICTED: Homosapiens similar to putative membrane-bound dipeptidase 2 (LOC339065)BC012289.1 KIAA0515 (KIAA0515) BC029444.1 immunoglobulin kappa constant(IGKC) BC015109.1 39S ribosomal protein L1, mitochondrial NM_024578.1occludin/ELL domain containing 1 (OCEL1) NM_003908.1 eukaryotictranslation initiation factor 2, subunit 2 beta, 38 kDa (EIF2S2)BC001726.1 Nucleolar protein 11 BC003666.2 NAD synthetase 1 (NADSYN1)NM_198491.1 family with sequence similarity 92, member B (FAM92B) PV3817WEE1 homolog (S. pombe) (WEE1) BC000974.2 WDR45-like (WDR45L) BC053675.1thymopoietin (TMPO) BC033292.1 interleukin 20 receptor beta (IL20RB)BC002509.1 PHD finger protein 23 BC006969.1 dynein, cytoplasmic 2, lightintermediate chain 1, mRNA (cDNA clone MGC: 12166 IMAGE: 3828551),complete cds BC069491.1 Cerberus NM_138559.1 B-cell CLL/lymphoma 11A(zinc finger protein) (BCL11A), transcript variant 3 BC004376.1 annexinA8 (ANXA8L1) NM_005620.1 S100 calcium binding protein A11 (S100A11)PV3872 epidermal growth factor receptor (erythroblastic leukemia viral(v- erb-b) oncogene homolog, avian) (EGFR); see catalog number fordetailed information on wild-type or point mutant status NM_032214.1Src-like-adaptor 2 (SLA2), transcript variant 1 NM_002444.1 moesin (MSN)NM_173796.2 hypothetical protein MGC24125 (MGC24125) NM_002648.1 pim-1oncogene (PIM1) NM_001876.2 Carnitine O-palmitoyltransferase 1, liverisoform BC014532.1 decapping enzyme, scavenger (DCPS) NM_001005266.1Dresden prostate carcinoma protein 2 NM_007172.2 nucleoporin 50 kDa(NUP50), transcript variant 2 NM_018326.1 GTPase, IMAP family member 4(GIMAP4) BC033881.1 XRCC6 binding protein 1 (XRCC6BP1) NM_020168.3p21(CDKN1A)-activated kinase 6 (PAK6) NM_014790.3 janus kinase andmicrotubule interacting protein 2 (JAKMIP2) NM_032360.1 acyl-Coenzyme Abinding domain containing 6 (ACBD6) NM_006303.2 JTV1 gene (JTV1)BC017305.1 sirtuin (silent mating type information regulation 2 homolog)7 (S. cerevisiae) (SIRT7) BC051762.1 Uncharacterized protein C20orf96NM_145010.1 chromosome 10 open reading frame 63 (C10orf63) NM_206834.1Uncharacterized protein C6orf201 BC009350.1 Eukaryotic translationinitiation factor 2-alpha kinase 4 NM_003720.1 Proteasome assemblychaperone 1 BC067755.1 potassium channel tetramerisation domaincontaining 18 (KCTD18) BC005840.2 selenoprotein S (SELS) BC000934.2eukaryotic translation initiation factor 2, subunit 2 beta, 38 kDa(EIF2S2) NM_020175.1 dihydrouridine synthase 3-like (S. cerevisiae)(DUS3L) BC014667.1 immunoglobulin heavy constant gamma 1 (G1m marker)(IGHG1) NM_201403.1 MOB1, Mps One Binder kinase activator-like 2C(yeast) (MOBKL2C), transcript variant 2 BC010537.1 SUB1 homolog (S.cerevisiae) (SUB1) NM_170746.2 Selenoprotein H NM_003092.3 small nuclearribonucleoprotein polypeptide B″ (SNRPB2), transcript variant 1NM_005105.2 RNA binding motif protein 8A (RBM8A) BC047411.1 tubulintyrosine ligase-like family, member 2 (TTLL2) NM_199188.1 Laribonucleoprotein domain family, member 4 (LARP4), transcript variant 2BC003551.1 transglutaminase 2 (C polypeptide, protein-glutamine-gamma-glutamyltransferase) (TGM2) BC020647.1 coiled-coil domain containing 59(CCDC59) BC011781.2 chromosome 9 open reading frame 37 (C9orf37)NM_032858.1 maelstrom homolog (Drosophila) (MAEL) NM_144971.1hypothetical protein MGC26641 (MGC26641) BC017440.1 trafficking proteinparticle complex 2-like (TRAPPC2L) BC017018.1 DnaJ (Hsp40) homolog,subfamily C, member 12 (DNAJC12) NM_144767.3 A kinase (PRKA) anchorprotein 13 (AKAP13), transcript variant 3 NM_018297.2 N-glycanase 1(NGLY1) NM_002307.1 lectin, galactoside-binding, soluble, 7 (galectin 7)(LGALS7) NM_003939.2 beta-transducin repeat containing (BTRC),transcript variant 2, mRNA. NM_013242.1 chromosome 16 open reading frame80 (C16orf80) NM_152285.1 arrestin domain containing 1 (ARRDC1)NM_178425.1 histone deacetylase 9 (HDAC9), transcript variant 5NM_007255.1 xylosylprotein beta 1,4-galactosyltransferase, polypeptide 7(galactosyltransferase I) (B4GALT7) NM_205833.1 immunoglobulinsuperfamily, member 1 (IGSF1), transcript variant 2 BC040457.1calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha(CAMK2A) NM_004732.1 potassium voltage-gated channel, shaker-relatedsubfamily, beta member 3 (KCNAB3) NM_004450.1 enhancer of rudimentaryhomolog (Drosophila) (ERH) XM_378582.2 PREDICTED: Homo sapienshypothetical LOC400523 (LOC400523) NM_001006666.1 apolipoprotein B mRNAediting enzyme, catalytic polypeptide-like 3F (APOBEC3F), transcriptvariant 2, mRNA. BC041876.1 tau tubulin kinase 2 (TTBK2) BC036335.1 BTB(POZ) domain containing 12 (BTBD12) BC036099.1 aryl-hydrocarbon receptornuclear translocator 2 (ARNT2) NM_054012.1 argininosuccinate synthetase1 (ASS1), transcript variant 2 NM_057749.1 cyclin E2 (CCNE2) PV3839CDC-like kinase 4 (CLK4) BC005026.1 sirtuin (silent mating typeinformation regulation 2 homolog) 6 (S. cerevisiae) (SIRT6) NM_013975.1ligase III, DNA, ATP-dependent (LIG3), nuclear gene encodingmitochondrial protein, transcript variant alpha NM_181509.1microtubule-associated protein 1 light chain 3 alpha (MAP1LC3A),transcript variant 2 BC001709.1 NAD kinase (NADK) NM_002638.1 peptidaseinhibitor 3, skin-derived (SKALP) (PI3) NM_005901.2 SMAD family member 2(SMAD2), transcript variant 1 BC046199.1 family with sequence similarity72, member B (FAM72B) NM_015417.2 sperm flagellar 1 (SPEF1) NM_018328.1methyl-CpG binding domain protein 5 (MBD5) BC017328.2 angiotensin IIreceptor-associated protein (AGTRAP) NM_182739.1 NADH dehydrogenase(ubiquinone) 1 beta subcomplex, 6, 17 kDa (NDUFB6), nuclear geneencoding mitochondrial protein, transcript variant 2 NM_001032293.1 zincfinger protein 207 (ZNF207), transcript variant 2 NM_012227.1 PutativeGTP-binding protein 6 BC026039.1 mitochondrial GTPase 1 homolog (S.cerevisiae) (MTG1) BC072409.1 Serine/threonine-protein phosphatase 4regulatory subunit 3A BC066938.1 DEAD (Asp-Glu-Ala-Asp) box polypeptide43 (DDX43) BC000712.1 kinesin family member C1 (KIFC1) BC000052.1peroxisome proliferator-activated receptor alpha (PPARA) NM_004117.2FK506 binding protein 5 (FKBP5) NM_002629.2 phosphoglycerate mutase 1(brain) (PGAM1) NM_015122.1 FCH domain only 1 (FCHO1) NM_001021.2ribosomal protein S17 (RPS17) NM_013323.1 sorting nexin 11 (SNX11),transcript variant 2 BC002950.1 chromosome 18 open reading frame 8(C18orf8) NM_017612.1 Zinc finger CCHC domain-containing protein 8BC035048.2 neurogenic differentiation 6 (NEUROD6) BC046117.1 dynein,axonemal, light intermediate chain 1 (DNALI1) NM_005335.3 Hematopoieticlineage cell-specific protein NM_144679.1 chromosome 17 open readingframe 56 (C17orf56) NM_004881.1 tumor protein p53 inducible protein 3(TP53I3), transcript variant 1 NM_199334.2 thyroid hormone receptor,alpha (erythroblastic leukemia viral (v- erb-a) oncogene homolog, avian)(THRA), transcript variant 1 NM_201567.1 cell division cycle 25 homologA (S. pombe) (CDC25A), transcript variant 2 BC012945.1 Uncharacterizedprotein C19orf57 BC043394.1 ankyrin repeat domain 17 (ANKRD17)NM_053005.2 HCCA2 protein (HCCA2) NM_175065.2 histone cluster 2, H2ab(HIST2H2AB) NM_004706.3 Rho guanine nucleotide exchange factor (GEF) 1(ARHGEF1), transcript variant 2 NM_014346.1 TBC1 domain family, member22A (TBC1D22A) NM_133480.1 transcriptional adaptor 3 (NGG1 homolog,yeast)-like (TADA3L), transcript variant 2 BC048969.1 TSPY-like 1(TSPYL1) NM_020319.1 ankyrin repeat and MYND domain containing 2(ANKMY2) NM_016046.2 exosome component 1 (EXOSC1) NM_001003396.1 tumorprotein D52-like 1 (TPD52L1), transcript variant 3 NM_005870.3 Histonedeacetylase complex subunit SAP18 NM_003403.3 YY1 transcription factor(YY1) BC036096.2 zinc finger protein 18 (ZNF18) NM_001010844.1Interleukin-1 receptor-associated kinase 1-binding protein 1 BC029524.1Coiled-coil domain-containing protein 46 NM_152387.2 BTB/POZdomain-containing protein KCTD18 BC002369.1 Serine/threonine-proteinkinase PLK1 BC092404.1 Rap guanine nucleotide exchange factor 3NM_004922.2 SEC24 related gene family, member C (S. cerevisiae)(SEC24C), transcript variant 1 NM_198217.1 Inhibitor of growth protein 1BC051911.1 chromosome 13 open reading frame 24 (C13orf24) NM_006205.1phosphodiesterase 6H, cGMP-specific, cone, gamma (PDE6H) NM_006439.3Protein mab-21-like 2 NM_173456.1 phosphodiesterase 8A (PDE8A),transcript variant 4 BC019268.1 Protein arginine N-methyltransferase 1NM_173642.1 family with sequence similarity 80, member A (FAM80A)NM_194299.1 Synaptonemal complex protein 2-like BC062323.1 chromosome 21open reading frame 25 (C21orf25) NM_021709.1 Apoptosis regulatoryprotein Siva BC100813.1 Putative T-complex protein 1 subunit theta-like2 BC026317.1 solute carrier family 16, member 1 (monocarboxylic acidtransporter 1) (SLC16A1) BC010956.1 Keratinocyte growth factorNM_005034.2 polymerase (RNA) II (DNA directed) polypeptide K, 7.0 kDa(POLR2K) BC024291.1 BR serine/threonine kinase 2 (BRSK2) NM_001001568.1phosphodiesterase 9A (PDE9A), transcript variant 3, mRNA. NM_014314.3Probable ATP-dependent RNA helicase DDX58 BC047420.1 UBXdomain-containing protein 7 NM_000430.2 platelet-activating factoracetylhydrolase, isoform Ib, alpha subunit 45 kDa (PAFAH1B1) PV3873epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) (EGFR); see catalog number for detailedinformation on wild-type or point mutant status NM_001328.1 C-terminalbinding protein 1 (CTBP1), transcript variant 1 NM_001009959.1 ErminBC050387.1 ankyrin repeat and sterile alpha motif domain containing 3(ANKS3) NM_007194.1 Serine/threonine-protein kinase Chk2 NM_018492.2 PDZbinding kinase (PBK) NM_182801.1 EGF-like, fibronectin type III andlaminin G domains (EGFLAM), transcript variant 4 BC016615.1 RAB37,member RAS oncogene family (RAB37) BC008950.2 Prenylated Rab acceptorprotein 1 BC041831.1 transducin-like enhancer of split 3 (E(sp1)homolog, Drosophila) (TLE3) NM_003104.2 sorbitol dehydrogenase (SORD)BC003555.1 nucleolar complex associated 2 homolog (S. cerevisiae)(NOC2L) NM_001274.2 CHK1 checkpoint homolog (S. pombe) (CHEK1)NM_153645.1 nucleoporin 50 kDa (NUP50), transcript variant 3 BC017423.1mesoderm induction early response 1 homolog (Xenopus laevis) (MIER1)BC007424.2 PRP4 pre-mRNA processing factor 4 homolog (yeast) (PRPF4)NM_007107.2 signal sequence receptor, gamma (translocon-associatedprotein gamma) (SSR3) XM_096472.2 hypothetical LOC143678 (LOC143678)NM_015698.2 G patch domain and KOW motifs (GPKOW) NM_018111.1 Putativeuncharacterized protein FLJ0490 NM_006694.1 jumping translocationbreakpoint (JTB) NM_000045.2 arginase, liver (ARG1) BC074765.2 POUdomain, class 6, transcription factor 1 NM_172028.1 ankyrin repeat andBTB (POZ) domain containing 1 (ABTB1), transcript variant 3 BC026345.1Ermin NM_201262.1 DnaJ (Hsp40) homolog, subfamily C, member 12(DNAJC12), transcript variant 2 NM_002966.1 S100 calcium binding proteinA10 (S100A10) BC013352.1 HpaII tiny fragments locus 9c proteinNM_004873.1 BCL2-associated athanogene 5 (BAG5), transcript variant 2BC009415.1 kinesin family member 26A (KIF26A) BC012539.1 mediatorcomplex subunit 31 (MED31) BC021247.1 Phosphatase and actin regulator 4NM_004414.3 regulator of calcineurin 1 (RCAN1), transcript variant 1BC028840.1 ankyrin repeat domain 13C (ANKRD13C) BC025787.1 alkB,alkylation repair homolog 1 (E. coli) (ALKBH1) NM_000459.1Angiopoietin-1 receptor NM_000788.1 Deoxycytidine kinase NM_173859.1breast cancer and salivary gland expression gene (RP11-49G10.8)NM_152382.1 JmjC domain-containing protein C2orf60 NM_002038.2interferon, alpha-inducible protein 6 (IFI6), transcript variant 1BC034984.1 Kinesin-like protein KIF16B NM_014582.1 odorant bindingprotein 2A (OBP2A) BC057760.1 MORN repeat-containing protein 3NM_005595.1 nuclear factor I/A (NFIA) NM_032726.1 phospholipase C, delta4 (PLCD4) NM_153276.1 solute carrier family 22 (organic aniontransporter), member 6 (SLC22A6), transcript variant 2 NM_001011538.1similar to 60S ribosomal protein L21 (LOC402176) NM_006433.2 granulysin(GNLY), transcript variant NKG5 NM_024800.1 Serine/threonine-proteinkinase Nek11 NM_015850.2 Basic fibroblast growth factor receptor 1NM_006590.2 ubiquitin specific peptidase 39 (USP39) NM_199054.1 MAPkinase interacting serine/threonine kinase 2 (MKNK2), transcript variant2 BC050696.1 chromosome 12 open reading frame 48 (C12orf48) NM_024563.1chromosome 5 open reading frame 23 (C5orf23) NM_004832.1 glutathioneS-transferase omega 1 (GSTO1) NM_003242.2 transforming growth factor,beta receptor II (70/80 kDa) (TGFBR2), transcript variant 2 BC050444.1golgi autoantigen, golgin subfamily a, 4 (GOLGA4) NM_201259.1Mitochondrial import inner membrane translocase subunit TIM14NM_032124.3 haloacid dehalogenase-like hydrolase domain containing 2(HDHD2) NM_002870.1 RAB13, member RAS oncogene family (RAB13) BC000337.2glucose-6-phosphate dehydrogenase (G6PD) BC060785.1 tripartitemotif-containing 40 (TRIM40) BC030597.1 ATR interacting protein (TREX1)BC050551.1 BCL2-associated athanogene 5 (BAG5) NM_004697.3 PRP4 pre-mRNAprocessing factor 4 homolog (yeast) (PRPF4) NM_020990.2 creatine kinase,mitochondrial 1B (CKMT1B), nuclear gene encoding mitochondrial proteinBC039742.1 poly(rC) binding protein 1 (PCBP1) BC021573.1 GTP-bindingprotein 10 NM_015068.1 paternally expressed 10 (PEG10), transcriptvariant 1 NM_001827.1 CDC28 protein kinase regulatory subunit 2 (CKS2)NM_152876.1 Tumor necrosis factor receptor superfamily member 6BC015548.1 RAB3A interacting protein (rabin3) (RAB3IP) BC062359.1chromosome 8 open reading frame 47 (C8orf47) BC029424.1 Probableglutathione peroxidase 8 NM_001786.2 cell division cycle 2, G1 to S andG2 to M (CDC2), transcript variant 1 BC000870.1 TIMELESS interactingprotein (TIPIN) NM_004103.2 Protein tyrosine kinase 2 beta BC022454.2Transient receptor potential cation channel subfamily M member 3NM_024046.1 CaM kinase-like vesicle-associated (CAMKV) BC040521.1 testisexpressed 2 (TEX2) BC003164.1 leukocyte receptor cluster (LRC) member 4(LENG4) NM_000402.2 Glucose-6-phosphate 1-dehydrogenase BC069328.1 Bcl2modifying factor (BMF) BC063463.1 coenzyme Q3 homolog, methyltransferase(S. cerevisiae) (COQ3) NM_000572.2 Interleukin-10 NM_006374.2serine/threonine kinase 25 (STE20 homolog, yeast) (STK25) NM_017966.1vacuolar protein sorting 37 homolog C (S. cerevisiae) (VPS37C)BC052602.1 carbonic anhydrase XIII (CA13) BC018063.1 potassium channeltetramerisation domain containing 4 (KCTD4) NM_031305.1 Rho GTPaseactivating protein 24 (ARHGAP24), transcript variant 2 BC056401.1centaurin, delta 2 (CENTD2) BC022459.1 sulfotransferase family 4A,member 1 (SULT4A1) XM_373630.2 PREDICTED: Homo sapiens hypotheticalprotein LOC145842 (LOC145842) P3049 v-abl Abelson murine leukemia viraloncogene homolog 1 (ABL1), transcript variant a; see catalog number fordetailed information on wild-type or point mutant status NM_153012.1Tumor necrosis factor ligand superfamily member 12 NM_018270.3MRG-binding protein BC010739.1 COP9 signalosome complex subunit 7bNM_015002.2 F-box protein 21 (FBXO21), transcript variant 2 BC000497.1CaM kinase-like vesicle-associated protein NM_001449.2 four and a halfLIM domains 1 (FHL1) BC065912.1 Tyrosine-protein kinase ABL2 NM_153356.1TBC1 domain family, member 21 (TBC1D21) BC032382.1 similar to pleckstrinhomology domain containing, family M (with RUN domain) member 1; adapterprotein 162, mRNA, complete cds. BC094800.1 Jouberin NM_003897.2immediate early response 3 (IER3) NM_178821.1 WD repeat domain 69(WDR69) NM_198219.1 Inhibitor of growth protein 1 NM_024805.1 chromosome18 open reading frame 22 (C18orf22) NM_001040633.1 protein kinase,AMP-activated, gamma 2 non-catalytic subunit (PRKAG2), transcriptvariant c, mRNA. NM_130807.1 MOB1, Mps One Binder kinase activator-like2A (yeast) (MOBKL2A) BC008623.1 roundabout, axon guidance receptor,homolog 3 (Drosophila) (ROBO3) NM_001004285.1 DNA fragmentation factor,40 kDa, beta polypeptide (caspase- activated DNase) (DFFB), transcriptvariant 3 BC011885.1 eukaryotic translation initiation factor 2A, 65 kDa(EIF2A)

In another preferred embodiment, the substrate and microarrays maycontain, as the autoantigen, at least one of the protein antigens ofTable 2, or a polypeptide or peptide fragment thereof containing one ormore epitopes recognized by the AD diagnostic autoantibody, or anepitope peptidomimetic that is recognized by the AD diagnosticautoantibody. The protein antigens in Tables 2-5 are identified byart-accepted names as well as database identification numbers. Thedatabase identification numbers refer to the publically availableprotein databases of the National Center for Biotechnology Information(NCBI) which are well-known and accessible to those of ordinary skill inthe art.

TABLE 2 Database ID Description BC030984.1 cDNA clone MGC: 32654 IMAGE:4701898, complete cds PHR5001 Recombinant human CTLA-4/Fc BC016380.1cDNA clone MGC: 27376 IMAGE: 4688477, complete cds BC015833.1 cDNA cloneMGC: 27152 IMAGE: 4691630, complete cds BC099907.1 General transcriptionfactor II-I BC051695.1 FERM domain containing 8 (FRMD8) BC040106.1hypothetical protein HSPC111 (HSPC111) NM_003141.2 tripartitemotif-containing 21 (TRIM21) NM_003384.1 vaccinia related kinase 1(VRK1) BC004236.2 ubiquitin-conjugating enzyme E2S (UBE2S) BC001662.1MAP kinase-activated protein kinase 3 NM_017588.1 WD repeat domain 5(WDR5), transcript variant 1 NM_032377.2 elongation factor 1 homolog (S.cerevisiae) (ELOF1) NM_021032.2 fibroblast growth factor 12 (FGF12),transcript variant 1 NM_000984.2 ribosomal protein L23a (RPL23A)BC064984.1 additional sex combs like 1 (Drosophila) (ASXL1) NM_012387.1peptidyl arginine deiminase, type IV (PADI4) NM_001641.2 APEX nuclease(multifunctional DNA repair enzyme) 1 (APEX1), transcript variant 1NM_001896.2 casein kinase 2, alpha prime polypeptide (CSNK2A2)NM_014481.2 APEX nuclease (apurinic/apyrimidinic endonuclease) 2(APEX2), nuclear gene encoding mitochondrial protein NM_014280.1 DnaJhomolog subfamily C member 8 BC007228.1 CSAG family, member 3A (CSAG3A)BC021174.1 Small EDRK-rich factor 1 BC033758.1 centaurin, alpha 2(CENTA2) BC005248.1 eukaryotic translation initiation factor 1A,Y-linked (EIF1AY) BC022098.1 cDNA clone MGC: 31944 IMAGE: 4878869,complete cds NM_024754.2 pentatricopeptide repeat domain 2 (PTCD2)NM_024316.1 leukocyte receptor cluster (LRC) member 1 (LENG1)NM_015920.3 40S ribosomal protein S27-like protein BC048970.1 tubulintyrosine ligase-like family, member 7 (TTLL7) NM_003668.2mitogen-activated protein kinase-activated protein kinase 5 (MAPKAPK5),transcript variant 1 NM_007278.1 GABA(A) receptor-associated protein(GABARAP) NM_006838.1 methionyl aminopeptidase 2 (METAP2) NM_018439.1Impact homolog (mouse) (IMPACT) NM_002013.2 FK506 binding protein 3, 25kDa (FKBP3) NM_018956.2 chromosome 9 open reading frame 9 (C9orf9)NM_004987.3 LIM and senescent cell antigen-like-containing domainprotein 1 BC004292.1 PHD finger protein 15 (PHF15) NM_133494.1 NIMA(never in mitosis gene a)-related kinase 7 (NEK7) NM_145063.1 chromosome6 open reading frame 130 (C6orf130) NM_021104.1 ribosomal protein L41(RPL41), transcript variant 1 NM_006223.1 protein (peptidylprolylcis/trans isomerase) NIMA-interacting, 4 (parvulin) (PIN4) NM_003135.1Signal recognition particle 19 kDa protein NM_015933.1 coiled-coildomain containing 72 (CCDC72) NM_001031.4 40S ribosomal protein S28BC022524.1 fibroblast growth factor 12 (FGF12) NM_001028.2 ribosomalprotein S25 (RPS25) NM_001997.2 Finkel-Biskis-Reilly murine sarcomavirus (FBR-MuSV) ubiquitously expressed (FAU) NM_080659.1 chromosome 11open reading frame 52 (C11orf52)

In another embodiment, the substrate and microarrays may contain, as theautoantigen, at least one of the protein antigens of Table 3, or apolypeptide or peptide fragment thereof containing one or more epitopesrecognized by the AD diagnostic autoantibodies, or an epitopepeptidomimetic that is recognized by the AD diagnostic autoantibody.

TABLE 3 Database ID Description BC051695.1 FERM domain-containingprotein 8 (FRMD8) NM_024754.2 Pentatricopeptide repeat-containingprotein 2 (PTCD2) NM_021104.1 60S ribosomal protein L41(RPL41)NM_032855.1 Hematopoietic SH2 domain-containing protein HSH2D

In another embodiment of one aspect of the present invention, themicroarray contains autoantigens consisting of FERM domain-containingprotein 8 (FRMD8), 60S ribosomal protein L41(RPL41), pentatricopeptiderepeat-containing protein 2 (PTCD2), and hematopoietic SH2domain-containing protein (HSH2D) or fragments thereof containing one ormore epitopes recognized by an AD diagnostic autoantibody, or epitopepeptidomimetics that are recognized by the AD diagnostic autoantibody.In another embodiment, the microarray contains autoantigens consistingof FERM domain-containing protein 8 (FRMD8) and hematopoietic SH2domain-containing protein (HSH2D) or fragments thereof containing one ormore epitopes recognized by an AD diagnostic autoantibody.

In one preferred embodiment of the present invention, the substrate andmicroarrays may contain, as the autoantigen, at least one of the proteinantigens of Table 4, or a fragment thereof containing one or moreepitopes recognized by an AD diagnostic autoantibody, or an epitopepeptidomimetic that is recognized by the AD diagnostic autoantibody. Inanother preferred embodiment of the present invention, the substrate andmicroarrays contain all of the protein antigens of Table 4.

TABLE 4 Database ID Description BC051695.1 FERM domain containing 8(FRMD8) NM_015833.1 adenosine deaminase, RNA-specific, B1 (RED1 homolograt) (ADARB1), transcript variant 2 NM_002305.2 lectin,galactoside-binding, soluble, 1 (galectin 1) (LGALS1) NM_001641.2 APEXnuclease (multifunctional DNA repair enzyme) 1 (APEX1), transcriptvariant 1 NM_024316.1 leukocyte receptor cluster (LRC) member 1 (LENG1)NM_014280.1 DnaJ homolog subfamily C member 8 PHC1244 chemokine (C-Cmotif) ligand 19 (CCL19) BC064984.1 additional sex combs like 1(Drosophila) (ASXL1) NM_021104.1 ribosomal protein L41 (RPL41),transcript variant 1 BC004236.2 ubiquitin-conjugating enzyme E2S (UBE2S)NM_012387.1 peptidyl arginine deiminase, type IV (PADI4) NM_003384.1vaccinia related kinase 1 (VRK1) NM_004113.3 fibroblast growth factor 12(FGF12), transcript variant 2 BC021174.1 Small EDRK-rich factor 1NM_001001794.1 family with sequence similarity 116, member B (FAM116B)NM_032377.2 elongation factor 1 homolog (S. cerevisiae) (ELOF1)NM_024754.2 pentatricopeptide repeat domain 2 (PTCD2) NM_000984.2ribosomal protein L23a (RPL23A) NM_139016.2 chromosome 20 open readingframe 198 (C20orf198) NM_024668.1 ankyrin repeat and KH domaincontaining 1 (ANKHD1), transcript variant 3Parkinson's Disease

In another embodiment of the present invention, the microarrays alsocontain autoantigens that are reactive with autoantibodies diagnosticfor Parkinson's Disease (PD) but not for AD, and thus permitdifferentiation of AD from PD. Autoantigens diagnostic for PD but not ADinclude, for example, the proteins of Table 5, and fragments thereofcontaining one or more epitopes recognized by a PD diagnosticautoantibody and epitope peptidomimetics that are recognized by the PDdiagnostic autoantibody.

TABLE 5 Database ID Description NM_003177.3 Spleen tyrosine kinase (SYK)BC_019015.2 Mediator of RNA polymerase II transcription subunit 29(MED29) BC003551 Protein-glutamine gamma-glutamyltransferase 2 (TGM2)PV3851 MAP/microtubule affinity-regulating kinase-4 (MAPrk4) BC001755.1Leiomodin-1

The following examples serve to further illustrate the presentinvention.

Example 1 Materials and Methods

Animals

Swiss-Webster mice were obtained from Taconic Farms (Hudson, N.Y.) andused for experiments at 3-6 months of age. Sprague-Dawley rats were alsoobtained from Taconic Farms and used at 7-9 weeks of age. Both weremaintained on ad libitum food and water with 12-hour light/dark cycle inan AALAC-accredited vivarium. Animals use was reviewed and approved bythe UMDNJ IACUC.

Human Brain Tissue

Brain tissue from patients with sporadic AD (n=23, age range=71-88) andage-matched, neurologically normal individuals (n=14, age range=69-83)were obtained from the Harvard Brain Tissue Resource Center (Belmont,Mass.), the Cooperative Human Tissue Network (Philadelphia, Pa.), theUCLA Tissue Resource Center (Los Angeles, Calif.) and Slidomics (CherryHill, N.J.). Post-mortem intervals were <24 h and pathologicalconfirmation of AD was evaluated according to criteria defined by theNational Institute on Aging and the Reagan Institute Working Group onDiagnostic Criteria for the Neuropathological Assessment of AD (Hymanand Trojanowski (1997) J Neuropathol Exp Neurol 56, 1095-7).Formalin-fixed tissues were processed for routine paraffin embedding andsectioning according to established protocols. Control tissues exhibitedminimal localized microscopic AD-like neuropathology.

Antibodies

Aβ42 antibodies were obtained from Millipore International (Temecula,Calif.,) (polyclonal, Cat. No. AB5078P, dilution=1:50) and Pharmingen(San Diego, Calif.) (polyclonal Cat. No. 4767, dilution=1:50).Biotinylated anti-human IgG antibodies for immunohistochemistry wereobtained from Vector Laboratories (Burlingame, Calif.) (host: goat, Cat.No. PK-6103, dilution=1:100). Peroxidase-conjugated anti-human IgGantibodies for western blotting were obtained from Thermo Scientific(Rockford, Ill.) (host: goat, Cat. No. 31410, dilution=1:200,000). Thefollowing antibodies were used for treatments of mouse organotypic brainslice cultures: anti-alpha7 nicotinic acetylcholine receptor (C-20,Santa Cruz Biotechnology, Santa Cruz, Calif.); anti-GluR2 (polyclonalN19, Santa Cruz Biotechnology, Santa Cruz, Calif.); anti-beta tubulin(D-10, Santa Cruz Biotechnology, Santa Cruz, Calif.). The specificity ofthese antibodies was confirmed by western blotting.

Human Sera

Human serum samples [AD (n=52, age range=61-97 years); age-matchedcontrols (n=28, age range=51-86); and younger healthy controls (n=28,age range=19-30 years)] were obtained from Analytical BiologicalServices Inc (Wilmington, Del.). Samples were numerically coded andincluded the following information: age and sex of the patient, thepresence or absence of a detectable neurological disease and, ifpresent, an indication of disease severity and estimated post-morteminterval. Use of these samples was approved by the UMDNJ IRB.

Immunohistochemistry

Immunohistochemistry was carried out using paraffin-embedded braintissues as previously described (D'Andrea et al. (2001) Histopathology38, 120-34; Nagele et al. (2002) Neuroscience 110, 199-211). Briefly,tissues were deparaffinized using xylene and rehydrated through a gradedseries of decreasing concentrations of ethanol. Antigenicity wasenhanced by microwaving sections in citrate buffer. Endogenousperoxidase was quenched by treating sections with 0.3% H₂O₂ for 30 min.Sections were incubated in blocking serum and then treated with primaryantibodies at appropriate dilutions for 1 hr at room temperature. Aftera thorough rinse in PBS, biotin-labeled secondary antibody was appliedfor 30 min. Sections were treated with the avidin-peroxidase complex(Vectastain ABC Elite, Vector Laboratories, Inc., Foster City, Calif.)and visualized with 3-3-diaminobenzidine-4-HCL (DAB)/H₂O₂ (1mm-Pact-DAB) (Vector). Sections were then lightly counterstained withhematoxylin, dehydrated through increasing concentrations of ethanol,cleared in xylene and mounted in Permount. Controls consisted of brainsections treated with non-immune serum or omission of the primaryantibody. Specimens were examined and photographed with a Nikon FXAmicroscope, and digital images were recorded using a Nikon DXM1200Fdigital camera and processed and analyzed using Image Pro Plus (Phase 3Imaging, Glen Mills, Pa.) and Cell Profiler image analysis softwares.

Preparation of Adult Rat Brain Proteins

To prepare rat brain protein fractions, fresh rat brain tissue wasremoved from storage at −80° C. and placed in a 1 mMphenylmethylsulfonyl fluoride, 50.0 mM Tris-HCL buffer solution, pH 7.4,at a 10.0 ml/g ratio along with protease inhibitor cocktail(Sigma-Aldrich, St. Louis, Mo.) at a 0.5 ml/g ratio. Using a pre-cooledDounce homogenizer (Arrow Engineering Co., Inc., Hillside, N.J.) at asetting of four, brain samples were subjected to homogenization. Brainsamples were then centrifuged at 3,000 rpm using a Beckman CS-6Rcentrifuge (Beckman Coulter Inc, Brea, Calif.) equipped with aswing-rotor at 4° C. for a period of 10 min to remove intact cells andlarge debris. The supernatant was retained as whole brain proteinfraction. Protein concentrations were determined using the BradfordAssay.

Detection of Autoantibody Targets Via Western Blotting

Western blot analysis was performed to determine the brain membranetargets of serum auto-antibodies. First, 12.5% SDS-polyacrylamideseparating gels were cast using the Mini PROTEAN 3 System (165-3302,BioRad, Hercules, Calif.) and overlain with stacking gels (4.0%). 100.0μg of protein sample was added to sample buffer and applied to the gelalongside PageRuler™ Prestained Protein Ladder Plus (SM1811, Fermentas,Glen Burnie, Md.). Proteins were then fractionated at 130V for 7minutes, followed by 100V for the remainder of the resolving time.Proteins were then transferred to Hybond-ECL Nitrocellulose Membrane(RPN3032D, Amersham, Piscataway, N.J.) for 75 minutes at 180 mA. Blotswere blocked in 5.0% non-fat dried milk dissolved in PBS-Tween (PBS-T)then transferred to human serum samples (primary antibody), diluted1:500 in blocking solution, for overnight incubation at 4° C. Thefollowing morning, blots were thoroughly rinsed in PBS-T then placed inthe appropriately diluted peroxidase-conjugated secondary antibody andincubated for one hour at 4° C. Blots were then thoroughly rinsed inPBS-T then quickly rinsed in dH₂O to remove phosphate buffer. Blots werethen developed using the Pierce enhanced chemiluminescence (ECL)substrate (32106, Pierce, Rockford, Ill.) and autoradiography film (XARALF 1824, Lab Scientific, Livingston, N.J.). Each western blot for agiven serum sample was performed in triplicate.

Mouse Organotypic Brain Slice Cultures and Treatments

Organotypic adult mouse brain slice cultures (MBOCs) were prepared usingthe technique of Stoppini et al. (1991) J Neurosci Methods. 37, 173-82.Neurons in these cultures have been shown to accumulate exogenous Aβ42(detectable within 4 h of exposure to 100 nM Aβ42) (Bahr et al., (1998)J Comp Neurol. 397, 139-47; Harris-White et al., (1998) J Neurosci. 18,10366-74; Malouf, (1992) Neurobiol Aging. 13, 543-51; Stoppini et al.(1991)). Brains from Swiss-Webster mice (3-6 months old) were isolatedunder sterile conditions and transverse coronal slices (0.5-0.75 mmthick) through desired brain regions were prepared using a Mcllwaintissue chopper, placed on 30 mm Millicell-CM culture inserts(Millicell-CM, Millipore, Bedford, Mass., USA), and allowed to stabilizein serum-free medium (DMEM) briefly (one hour) or in 25% inactivatedhorse serum, 25% Hanks' BSS, 50% DMEM, 25 mg/l penicillin-streptomycin)overnight prior to treatment. Following stabilization, cultures wereexposed to serum-free medium (DMEM alone) or complete medium (25%inactivated horse serum, 25% Hanks' BSS, 50% DMEM, 25 mg/lpenicillin-streptomycin) containing Aβ42 peptide (100 nM), anti-GluR2antibody (diluted 1:250), human serum samples (diluted 1:50),anti-α7nAChR antibody (diluted 1:1000), anti-β-tubulin antibody (diluted1:200). Control slices received medium only. MBOCs were treated for upto 72 h at 37° C. in a 5% CO₂-enriched atmosphere. Aβ42 was solubilizedto the monomeric form using the method of (Zagorski et al. (1999)Methods Enzymol. 309, 189-204).

Image Analysis

The extent of Aβ42 accumulation in MBOCs treated with 100 nM Aβ42 withor without human serum or antibodies directed against the α7nAChR orGluR2 was determined using quantitative immunohistochemistry. MBOCstreated as described above were first immunostained with anti-Aβ42antibodies under identical conditions. Images were then recorded underidentical illumination and camera settings using a Nikon FXA microscopeequipped with a Nikon CCD camera and image analysis softwares (Image ProPlus and Cell Profiler). Relative amounts of intracellular Aβ42-positivedeposit per Aβ42-positive cell were determined and compared among thedifferent treatment groups. The significance of differences in theamount of intracellular Aβ42 within cells were determined by theStudent's t-test. Controls for immunohistochemistry included nonimmuneserum or detection antibody only.

Example 2 Brain Reactive Autoantibodies in Human Sera

Sera from AD patients (n=52, age range 61-97 years), age-matched,non-demented control subjects (n=28, age range 51-86 years) and youngerhealthy individuals (n=28, age range 19-30 years) were tested for thepresence of brain-reactive autoantibodies. For western analyses,individual sera were tested for the presence of brain-reactiveautoantibodies by probing proteins obtained from whole cell homogenatederived from adult rat brain. Results confirmed the presence ofbrain-reactive autoantibodies in all sera from the three groups tested.The number of immunoreactive protein bands generated by each serumsample was similar for all three subject groups: mean=5.1+/−3.1 for ADsera (n=52); 7.4+/−4.0 for age-matched control sera (n=28); and6.0+/−3.8 for younger healthy control sera (n=28). Comparable resultswere obtained when human sera were used to probe mouse and human brainproteins. Based on apparent molecular weights in western blots, a fewpotentially common protein bands were noted within and among the threesubject groups.

Example 3 IgG-Positive Neurons in Brain Regions Exhibiting AD Pathology

Ig-positive neurons in postmortem AD brains have been reported (Bouraset al. (2005) Brain Res Brain Res Rev. 48, 477-87; Clifford et al.(2007) Brain Res. 1142, 223-36; Deane and Zlokovic (2007) Curr AlzheimerRes. 4, 191-7; Franceschi et al. (1989) J. Gerontol. 44, M128-30;Kalaria (1999) Ann NY Acad. Sci. 893, 113-125; Kulmala et al. (1987) ExpAging Res 13:67-72; Loeffler et al. (1997) Neurochem Res. 22, 209-14;Mooradian (1988) Neurobiol Aging. 9, 31-9; Nandy et al. (1975) J.Gerontol. 30, 269-74; Stein et al. (2002) J Neuropathol Exp Neurol. 61,1100-8). In this example, immunohistochemistry using anti-human IgGantibodies was employed to test for the presence of IgG-immunopositivebrain components in 23 AD and 14 age-matched control brains.IgG-positive neurons with immunolabeled cell bodies and dendrite trunkswere found in all brains that were examined. IgG-positive neurons werefar more abundant, widespread and intensely immunostained in AD brainsthan in corresponding age-matched control brains. In the latter,IgG-positive neurons were most often encountered as scattered individualcells and small cell clusters separated by relatively large expanses ofbrain tissue that were completely devoid of IgG-positive cells. In ADbrains, IgG-positive neurons were particularly abundant in brain regionsknown to be vulnerable to AD-associated pathological changes (e.g.,temporal cortex, entorhinal cortex and hippocampus). In both AD andcontrol brains, IgG immunoreactivity was consistently and preferentiallyassociated with pyramidal neurons, and these cells often showed markedindividual variations in the intensity of IgG immunolabeling, sometimeswith IgG-positive and -negative neurons present in close proximity.Similar variations in neuronal IgG immunostaining intensity were notedin neurons of the hippocampus. In pyramidal neurons, IgGimmunoreactivity was most conspicuous in the cell body and proximalsegment of the main dendrite trunk. Most of the smaller neurons,astrocytes and microglia that were interspersed among pyramidal cellswere IgG-negative. In three of the 23 AD brains examined, bothastrocytes and pyramidal neurons were IgG-positive, but this was notobserved in age-matched control brains.

Example 4 Relationship Between IgG Immunoreactivity and Aβ42 Deposition

Sections of post-mortem AD brain tissue were probed with antibodiesspecific for human IgG and Aβ42. In regions of the cerebral cortex andhippocampus showing mild AD pathology (i.e., regions with sequesteredintraneuronal Aβ42 deposits but few amyloid plaques),Aβ42-immunopositive neurons also exhibited intense IgG immunostaining.Two sets of consecutive sections were immunostained to reveal therelative distribution of Aβ42 and IgG in the cerebral cortex of ADbrains. In regions exhibiting mild AD pathology, both IgG and Aβ42 werecolocalized to the same neurons appearing in both sections. Likewise, incortical regions showing more advanced pathology (as judged by theincreased deposition of Aβ42 within neurons and amyloid plaques), theamount of interstitial and intraneuronal IgG was substantiallyincreased. In addition to the typical large juxtanuclear deposits ofAβ42-rich material in pyramidal neurons, the main dendrite trunks ofthese cells frequently contained abundant small Aβ42-positive granulesof uniform size. These results demonstrate the temporal and spatialcoincidence of intraneuronal Aβ42 deposition and IgG immunolabelingwithin pyramidal neurons.

Example 5 Reactivity of Human Serum Antibodies with Living Neurons

To test for the reactivity (i.e., binding) of human serum antibodieswith the surfaces of living neurons, adult mouse brain organotypic(brain slice) cultures (MBOCs) were maintained in medium with or withoutdiluted human serum for up to 72 h. MBOCs retain the adult brainhistological architecture for up to several weeks under properconditions and have been shown to contain neurons that internalize andaccumulate exogenous, soluble Aβ42 peptide (Bahr et al. (1998);Harris-White et al. (1998); Malouf (1992); Stoppini et al. (1991). Thebinding of human IgG to neurons in MBOCs was detected byimmunohistochemistry using anti-human IgG antibodies. Addition of humanserum to the culture medium resulted in intense and selective IgGimmunolabeling of living adult mouse neurons, whereas controls nottreated with serum showed no inherent IgG immunoreactivity. The patternof background IgG immunostaining in human serum-treated MBOCs suggeststhat dendrites and/or synaptic connections may also be IgG-positive. Aswas shown in postmortem human AD brains described above, pyramidalneurons of the cerebral cortex of MBOCs were consistently the mostintensely immunopositive cells.

Example 6 Effect of Autoantibodies on Internalization of Exogenous Aβ42

This example utilizes the property of cross-reactivity of the antibodiesin human serum with rodent brain proteins as demonstrated above inwestern blots and in brain tissue as shown above in immunohistochemicalpreparations. MBOCs were treated with 100 nM Aβ42 in the presence orabsence of individual human serum samples diluted 1:50 in otherwiseserum-free medium for 1, 3, 24, 48 and 72 h and the relative amounts ofintraneuronal Aβ42 were quantified using image analysis for MBOCstreated for 24 h. MBOCs treated with 100 nM Aβ42 alone for 24 h showedno human IgG immunostaining and only minimal Aβ42 immunoreactivity. Onthe other hand, when MBOCs were exposed to human serum autoantibodiesand Aβ42 peptide for 24 h, pyramidal neurons selectively showed adramatic increase in intracellular Aβ42 accumulation over that ofcontrols treated with Aβ42 peptide or serum alone for the same timeperiod. Within these neurons, Aβ42-positive material was localized todense cytoplasmic granules that were concentrated in the neuronalperikaryon and proximal dendrite trunk. Measurements of the relativeamounts of intraneuronal Aβ42 in MBOCs using image analysis after 24 hof treatment revealed that the addition of human serum to mediumcontaining 100 nM Aβ42 caused a many-fold increase in neuronal Aβ42immunoreactivity over that in cells treated with Aβ42 alone.Morphological evidence of significant cell death and loss ofAβ42-burdened neurons in MBOCs was not observed

Example 7 Effect of Purified Antibodies Targeting Neural SurfaceProteins on Internalization of Exogenous Aβ42

MBOCs were treated for 24 h with commercially available antibodiesdirected against two neuronal receptors that are known to be abundantlyexpressed on neuronal cell surfaces, the alpha7 nicotinic acetylcholinereceptor (α7nAChR) and the glutamate R2 (GluR2) receptor. Bothantibodies were found to be effective in increasing intraneuronal Aβ42accumulation, again selectively in pyramidal neurons and well abovelevels seen in cultures treated with Aβ42 alone. To explore whetherneuronal cell surface reactivity of IgG is required for enhancement ofexogenous Aβ42 internalization, MBOCs were also treated with an antibodydirected against the common intracellular protein, beta-tubulin, alongwith 100 nM Aβ42. Treatment with beta-tubulin antibody resulted inlevels of neuronal Aβ42 accumulation that were comparable to treatmentwith 100 nM Aβ42 alone.

Example 8 Identification of Autoantibodies Diagnostic for AD

Western Analysis

As disclosed hereinabove, biochemical confirmation of the presence ofbrain-reactive autoantibodies in individual human sera was carried outusing western analysis. In addition, total rat brain protein, which isimmunoreactive to human autoantibodies as shown hereinabove, was used tocompare sera from patients with AD, age-matched neurologically normalcontrols and younger healthy individuals. Based on estimated molecularweights alone, the resulting distributions of molecular weights forindividual target proteins were analyzed using the pattern recognitioncomputer program called A.I. Solver (Silversoft Solutions).

Based on the recognition of specific patterns of distribution ofmolecular weights of autoantibody target proteins, A.I. Solver was ableto distinguish western blots derived from AD patient's sera from that ofage-matched controls and younger healthy subjects 98% of the time. Thisexample demonstrates the existence of AD-specific protein antibodies inthe blood that bind to brain protein target antigens. Next, a proteinmicroarray platform was used identify the specific subset ofautoantibodies and their target proteins that are useful to effectivelydiagnose AD.

Microarray Procedure

The protein microarray platform used to identify diagnostic antibodiesand prove the efficacy of a protein microarray diagnostic wasInvitrogen's ProtoArray® Human Protein Microarray v5.0. It is ahigh-density protein microarray containing thousands of purified humanproteins for protein interaction screening. Each human open readingframe (ORF) is expressed as an N-terminal GST fusion protein using abaculovirus expression system, purified from insect cells, and printedin duplicate on a nitrocellulose-coated glass slide. The Immune ResponseBiomarker Profiling application was used as it is best suited the needsof a diagnostic. All reagents and materials were purchased directlythrough Invitrogen. The recommended Invitrogen Prot® Array® protocol wasstrictly adhered to at all times and is incorporated herein by referencein its entirety. The array was probed with diluted (1:500) human serumor plasma.

Microarray Scanning

The protein microarrays were scanned using the recommended Axon Genepix4000b imager. Individual slides were inserted into the imager and thenscanned using 100% laser power, 635 nm excitation wavelength, PMT 600,and Sum pixel size. Data was extracted from the image by syncing it witha Genepix Array List (.GAL) file obtained from Invitrogen. GAL filesdescribe the location and identity of all spots on the proteinmicroarray and are used by Genepix Pro software (by Molecular Devices)to generate files that contain pixel intensity information for allfeatures on the array. Genepix Pro then creates a .GPR (Genepix PixelResults) file that lists all of the pixel intensity data for eachprotein spot on the microarray in text-only spreadsheet format. It isthe GPR file that is imported into Prospector for data analysis.

Normalization

After acquiring the individual microarray data by scanning themicroarrays with an Axon Genepix 4000b imager and performing the initialquantification with Genepix Pro software, the resulting data werenormalized so as to allow microarray-to-microarray comparison. For this,Invitrogen's proprietary software, Prospector; more specifically, theImmune Response Biomarker Profiling Toolbox application, was used. Eachmicroarray's gpr file was imported into the program, analyzed, andnormalized to a linear model.

Fitting the data to a linear model was performed through a robustregression by means of an iteratively re-weighted least-square procedurewith an M-estimator, like the median. The linear model useslog-transformed signals to estimate and correct the variations. For eachspot replicate r (=1, 2) of protein feature k (=1, . . . , n_(f)) insub-array j (=1, . . . , 48) on slide i (=1, . . . , n_(s),) thefollowing model was fit:y _(ijkr)=α_(i)+β_(j)+τ_(k)+ε_(ijkr)where y_(ijkr) is the observed signal in log 2 scale, α is the slideeffect, β_(j) is the sub-array/block effect (including printing pineffect), τ_(k) is the “true” signal of the protein feature (differentprotein content printed in different concentration), and ε_(ijkr) theerror, assuming ε_(ijkr)˜N(0,σ²). After the coefficients of theseeffects were estimated using control proteins, the normalized signal inits original scale for each spot was calculated as:S _(ijkr)=2^(y _(ijkr)−α_(i)−β_(j))

After normalization, the microarray data was fully adjusted for errorand individual variation; formal analysis was begun. It was thisadjusted data from which diagnostic significance was determined.

Data Analysis

There are multiple accepted methods of determining the diagnosticsignificance of microarray fluorescence data. To ensure thereproducibility and accuracy of our results, data were analyzed threeseparate times using three independent and distinct methods. The methodschosen are among the most reliable and consistent available, and arecommonly used in similar studies. The methods are: M-StatisticalPrevalence, Nearest Shrunken Centroid Analysis, and Random ForestDecision-Making Trees. To harness each of these unbiased statisticalquantification schemes, Prospector, PAM, and R's Random Forest,respectively, were utilized. Each of these programs evaluated theprotein microarray data to determine which proteins were mostsignificant to diagnose Alzheimer's Disease. The lists reflected oneanother almost exactly, thus demonstrating that protein microarrays areuseful as a successful diagnostic. The statistical methods, programsinvolved, and results generated are described below.

M-Statistical Analysis

As well as interpreting and normalizing the raw fluorescence datagenerated by Genepix Pro, Prospector was used to generate M-Statisticsthat were, in turn, used to evaluate each protein's diagnosticsignificance. Briefly, M-statistics were used to determine the number ofassays in one group (e.g. Alzheimer's or Control) that have a signalvalue for a protein greater than the highest observed signal value ofthis probe in the comparison group. The M order statistic for the groupy of size n_(y) compared to group x of size n_(x) is given by theformula:M ^(y) _(i,above,between)=Σ1_({yk>x(i)+between})1_({yk>above})where x_((i)) is the i_(th) largest value of the group x, and above andbetween are the calculation parameters. A p-value was calculated as theprobability of having M value greater or equal than M_(i). Prospectorselected the M statistic with the lowest p-value and reported thisM_(max) value and order, as well as a corresponding p-value and proteinprevalence estimate. The values were viewed as a spreadsheet inMicrosoft Excel Workbook format, and filtered to provide a list of themost effective indicators of group differences, i.e., the proteins thatare the best diagnostic markers.PAM (Prediction Analysis of Microarrays)

Another method of interpreting protein microarray results and yieldingprotein significance is PAM, or Prediction Analysis of Microarrays. PAMis a statistical technique for class prediction that uses nearestshrunken centroids. It is run as a Microsoft Excel Macro and has beenused extensively in characterizing microarray results (Tibshirani et al.(2002) Proc Natl Acad Sci USA 99:6567-6572). The program was used toidentify specific subsets of fluorescence data that best characterizeeach class and thus serve as significant diagnostic indicators. Briefly,the method computed a standardized centroid for each class. This is theaverage fluorescence for protein in each class divided by thewithin-class standard deviation for that protein. Centroids were“shrunken”—reduced by a threshold value—to reduce error and outliereffect. The microarray fluorescence of each new sample was then comparedto each shrunken class centroid; the class whose centroid that it wasclosest to, in squared distance, was the predicted class for that newsample. Using this information, PAM generated a list of proteinspresented in order of diagnostic significance.

PAM was used to produce a list of the top fifty most important proteinsfor distinguishing Alzheimer's Disease sera from Control Sera which isshown below in Table 6.

TABLE 6 Protein AD Control database ID Description score scoreBC030984.1 cDNA clone MGC: 32654 IMAGE: 4701898, 0.2132 −0.2665 completecds PHR5001 Recombinant human CTLA-4/Fc 0.2108 −0.2635 BC016380.1 cDNAclone MGC: 27376 IMAGE: 4688477, 0.1766 −0.2208 complete cds BC015833.1cDNA clone MGC: 27152 IMAGE: 4691630, 0.1621 −0.2026 complete cdsBC099907.1 General transcription factor II-I −0.156 0.195 BC051695.1FERM domain containing 8 (FRMD8) 0.1452 −0.1816 BC040106.1 hypotheticalprotein HSPC111 (HSPC111) 0.1429 −0.1787 NM_003141.2 tripartitemotif-containing 21 (TRIM21) 0.1388 −0.1735 NM_003384.1 vaccinia relatedkinase 1 (VRK1) 0.1268 −0.1585 BC004236.2 ubiquitin-conjugating enzymeE2S (UBE2S) 0.1244 −0.1555 BC001662.1 MAP kinase-activated proteinkinase 3 0.1183 −0.1479 NM_017588.1 WD repeat domain 5 (WDR5),transcript variant 1 0.1176 −0.147 NM_032377.2 elongation factor 1homolog (S. cerevisiae) (ELOF1) 0.1158 −0.1448 NM_021032.2 fibroblastgrowth factor 12 (FGF12), transcript 0.1144 −0.143 variant 1 NM_000984.2ribosomal protein L23a (RPL23A) 0.1123 −0.1403 BC064984.1 additional sexcombs like 1 (Drosophila) (ASXL1) 0.1106 −0.1383 NM_012387.1 peptidylarginine deiminase, type IV (PADI4) 0.1082 −0.1353 NM_001641.2 APEXnuclease (multifunctional DNA repair 0.1062 −0.1327 enzyme) 1 (APEX1),transcript variant 1 NM_001896.2 casein kinase 2, alpha primepolypeptide (CSNK2A2) 0.1045 −0.1306 NM_014481.2 APEX nuclease(apurinic/apyrimidinic endonuclease) −0.1009 0.1261 2 (APEX2), nucleargene encoding mitochondrial protein NM_014280.1 DnaJ homolog subfamily Cmember 8 0.0993 −0.1242 BC007228.1 CSAG family, member 3A (CSAG3A)0.0952 −0.119 BC021174.1 Small EDRK-rich factor 1 0.0924 −0.1155BC021174.1 Small EDRK-rich factor 1 0.0924 −0.1155 BC033758.1 centaurin,alpha 2 (CENTA2) 0.0894 −0.1118 BC005248.1 eukaryotic translationinitiation factor 1A, Y-linked 0.0876 −0.1096 (EIF1AY) BC022098.1 cDNAclone MGC: 31944 IMAGE: 4878869, 0.0853 −0.1066 complete cds NM_024754.2pentatricopeptide repeat domain 2 (PTCD2) 0.0845 −0.1057 NM_024316.1leukocyte receptor cluster (LRC) member 1 (LENG1) −0.0836 0.1044NM_015920.3 40S ribosomal protein S27-like protein 0.0798 −0.0997BC048970.1 tubulin tyrosine ligase-like family, member 7 0.0792 −0.099(TTLL7) NM_003668.2 mitogen-activated protein kinase-activated protein0.0789 −0.0986 kinase 5 (MAPKAPK5), transcript variant 1 NM_007278.1GABA(A) receptor-associated protein (GABARAP) 0.0787 −0.0984 NM_006838.1methionyl aminopeptidase 2 (METAP2) 0.0779 −0.0974 NM_018439.1 Impacthomolog (mouse) (IMPACT) 0.0772 −0.0965 NM_002013.2 FK506 bindingprotein 3, 25 kDa (FKBP3) 0.0749 −0.0937 NM_018956.2 chromosome 9 openreading frame 9 (C9orf9) 0.0744 −0.093 NM_004987.3 LIM and senescentcell antigen-like-containing −0.0741 0.0926 domain protein 1 BC004292.1PHD finger protein 15 (PHF15) −0.0709 0.0886 NM_133494.1 NIMA (never inmitosis gene a)-related kinase 7 0.0699 −0.0874 (NEK7) NM_145063.1chromosome 6 open reading frame 130 (C6orf130) 0.0646 −0.0808NM_021104.1 ribosomal protein L41 (RPL41), transcript variant 1 0.0645−0.0807 NM_006223.1 protein (peptidylprolyl cis/trans isomerase) NIMA-0.0633 −0.0791 interacting, 4 (parvulin) (PIN4) NM_003135.1 Signalrecognition particle 19 kDa protein 0.0622 −0.0777 NM_015933.1coiled-coil domain containing 72 (CCDC72) 0.0615 −0.0769 NM_001031.4 40Sribosomal protein S28 0.0606 −0.0758 BC022524.1 fibroblast growth factor12 (FGF12) 0.0594 −0.0743 NM_001028.2 ribosomal protein S25 (RPS25)0.0578 −0.0722 NM_001997.2 Finkel-Biskis-Reilly murine sarcoma virus(FBR- 0.0572 −0.0715 MuSV) ubiquitously expressed (FAU) NM_080659.1chromosome 11 open reading frame 52 (C11orf52) 0.0566 −0.0707

Random Forest

The third quantitative method that was used to corroborate the resultswas Random Forest. This is an open-source classification algorithm, runthrough R, that uses an ensemble of decision-making trees. Each of theseclassification trees was built using a bootstrap sample of the data, andat each split the candidate set of variables was a random subset. RandomForest directly returned several measures of variable significance,which were related to the relevance of the variable in theclassification. Hence, in this case, it provided an evaluation of eachprotein's relative importance to proper diagnosis.

The most reliable measure was based on the decrease of classificationaccuracy when values of a variable in a node of a tree were permutedrandomly and this was the measure of variable importance. Anotherestimation of significance of a variable was based on Gini impurity.Every time a split of a node was made on variable m the Gini impuritycriterion for the two descendent nodes was less than the parent node.Adding up the Gini decreases for each individual variable over all treesin the forest gave a fast variable importance that is often veryconsistent with the permutation importance measure.

The Relative Fluorescence Unit value for each protein spot on themicroarray, as calculated by Genepix Pro and Prospector, was importedinto Random Forest. The prediction model was performed using the Rpackage and all default settings—as is proscribed for the bestmicroarray analysis results. Calculating an average Out-Of-Bag Error ofonly 6.67%, the algorithm was able to quickly evaluate proteinsignificance based on the evaluation methods described above.

Results

Three different, unbiased statistical methods were used to evaluate thediagnostic significance of individual autoantibodies in the microarraydata and they reflected one another almost perfectly. The threeresultant lists considered the same autoantibodies diagnosticallyimportant, and assigned them similar significance. The sharedconclusions of all three lend the results great confidence. The list ofall of the protein antigens determined by these methods that haveautoantibodies that can be used as indicators for Alzheimer's disease isshown below in Table 7. Included is the protein database identificationnumber, the open reading frame number, the common name for each protein,its disease-state indication, and the relevant p-value as calculated bythe M-statistic.

TABLE 7 Ultimate Database ID ORF ID Description Indication P-ValueNM_024754.2 IOH12500 pentatricopeptide repeat domain 2 AD 8.03E−14(PTCD2) BC051695.1 IOH26532 FERM domain containing 8 AD 4.06E−13 (FRMD8)NM_014280.1 IOH42939 DnaJ homolog subfamily C AD 9.49E−12 member 8BC064984.1 IOH40665 additional sex combs like 1 AD 6.02E−11 (Drosophila)(ASXL1) BC030814.1 IOH23035 immunoglobulin kappa variable 1- Control7.00E−11 5 (IGKV1-5) NM_003384.1 IOH41408 vaccinia related kinase 1(VRK1) AD 2.03E−10 NM_001544.2 IOH23172 intercellular adhesion molecule4 AD 2.03E−10 (Landsteiner-Wiener blood group) (ICAM4), transcriptvariant 1 NM_001896.2 IOH6369 casein kinase 2, alpha prime AD 2.51E−10polypeptide (CSNK2A2) NM_021104.1 IOH13630 ribosomal protein L41(RPL41), AD 4.61E−10 transcript variant 1 BC016380.1 IOH23077 cDNA cloneMGC: 27376 AD 5.14E−10 IMAGE: 4688477, complete cds NM_012387.1 IOH11317peptidyl arginine deiminase, type AD 6.53E−10 IV (PADI4) NM_003135.1IOH59899 Signal recognition particle 19 kDa AD 8.77E−10 proteinBC022524.1 IOH10757 fibroblast growth factor 12 AD 8.77E−10 (FGF12)BC000758.1 IOH3735 Coiled-coil domain-containing AD 1.45E−09 protein 28ANM_021032.2 IOH35339 fibroblast growth factor 12 AD 1.45E−09 (FGF12),transcript variant 1 NM_022343.2 IOH59950 Golgi-associated plant AD1.49E−09 pathogenesis-related protein 1 BC004236.2 IOH3887ubiquitin-conjugating enzyme E2S AD 2.00E−09 (UBE2S) NM_000983.3IOH58958 60S ribosomal protein L22 AD 2.05E−09 NM_017588.1 IOH4895 WDrepeat domain 5 (WDR5), AD 2.88E−09 transcript variant 1 NM_018956.2IOH11209 chromosome 9 open reading frame AD 3.30E−09 9 (C9orf9)BC033178.1 IOH23236 immunoglobulin heavy constant AD 4.07E−09 gamma 3(G3m marker) (IGHG3) NM_006628.4 IOH3044 cyclic AMP phosphoprotein, 19kD AD 4.19E−09 (ARPP-19) BC022098.1 IOH14790 cDNA clone MGC: 31944 AD4.19E−09 IMAGE: 4878869, complete cds NM_001641.2 IOH5081 APEX nuclease(multifunctional AD 5.85E−09 DNA repair enzyme) 1 (APEX1), transcriptvariant 1 NM_003668.2 mitogen-activated protein kinase- AD 8.91E−09activated protein kinase 5 (MAPKAPK5), transcript variant 1 NM_015933.1IOH3769 coiled-coil domain containing 72 AD 8.91E−09 (CCDC72) PHC1244chemokine (C-C motif) ligand 19 AD 9.85E−09 (CCL19) BC099907.1 IOH62625General transcription factor II-I Control 1.09E−08 BC007782.2 IOH6514immunoglobulin lambda constant AD 1.09E−08 1 (Mcg marker) (IGLC1)BC006423.1 Serine/threonine-protein kinase 6 AD 1.34E−08 BC042628.1IOH27650 serpin peptidase inhibitor, clade E AD 1.34E−08 (nexin,plasminogen activator inhibitor type 1), member 2 (SERPINE2) BC021561.1IOH14131 FACT complex subunit SPT16 AD 1.34E−08 BC005248.1 IOH7358eukaryotic translation initiation AD 1.34E−08 factor 1A, Y-linked(EIF1AY) NM_006223.1 IOH7192 protein (peptidylprolyl cis/trans AD1.34E−08 isomerase) NIMA-interacting, 4 (parvulin) (PIN4) NM_032377.2IOH6191 elongation factor 1 homolog (S. cerevisiae) AD 1.34E−08 (ELOF1)BC057774.1 IOH29168 RNA (guanine-9-)- AD 1.52E−08 methyltransferasedomain- containing protein 3 NM_004196.2 Cyclin-dependent kinase-like 1AD 1.64E−08 BC001662.1 MAP kinase-activated protein AD 2.32E−08 kinase 3NM_015920.3 IOH57353 40S ribosomal protein S27-like AD 2.32E−08 proteinNM_001031.4 IOH58930 40S ribosomal protein S28 AD 2.62E−08 NM_003688.1Peripheral plasma membrane AD 2.62E−08 protein CASK BC048970.1 IOH26893tubulin tyrosine ligase-like family, AD 3.23E−08 member 7 (TTLL7)NM_000984.2 IOH13591 ribosomal protein L23a (RPL23A) AD 3.23E−08NM_018439.1 IOH23069 Impact homolog (mouse) AD 3.76E−08 (IMPACT)NM_002305.2 IOH3861 lectin, galactoside-binding, AD 3.76E−08 soluble, 1(galectin 1) (LGALS1) BC056508.1 IOH29456 variable charge, Y-linked 1BAD 4.13E−08 (VCY) BC090938.1 IOH62696 Ig gamma-1 chain C region AD4.45E−08 NM_002013.2 IOH14109 FK506 binding protein 3, 25 kDa AD4.51E−08 (FKBP3) NM_007278.1 IOH41289 GABA(A) receptor-associated AD4.51E−08 protein (GABARAP) BC007228.1 IOH6059 CSAG family, member 3A AD4.51E−08 (CSAG3A) BC033758.1 IOH21879 centaurin, alpha 2 (CENTA2) AD5.27E−08 BC092518.1 IOH62695 Ig gamma-1 chain C region AD 6.86E−08BC019598.1 IOH10613 Zinc finger matrin-type protein 4 AD 7.00E−08NM_145909.1 IOH45888 Zinc finger protein 323 AD 7.00E−08 NM_003516.2IOH4867 histone cluster 2, H2aa3 AD 7.22E−08 (HIST2H2AA3) NM_006838.1IOH11106 methionyl aminopeptidase 2 AD 7.36E−08 (METAP2) BC026038.1IOH13982 Ig gamma-1 chain C region AD 1.01E−07 NM_002129.2 IOH3826high-mobility group box 2 AD 1.01E−07 (HMGB2) NM_002677.1 IOH27101peripheral myelin protein 2 AD 1.16E−07 (PMP2) BC001132.1 IOH3853 DEAD(Asp-Glu-Ala-Asp) box AD 1.27E−07 polypeptide 54 (DDX54) NM_001001794.1IOH27259 family with sequence similarity AD 1.27E−07 116, member B(FAM116B) NM_001997.2 IOH1655 Finkel-Biskis-Reilly murine AD 1.27E−07sarcoma virus (FBR-MuSV) ubiquitously expressed (FAU) BC021174.1IOH10706 Small EDRK-rich factor 1 AD 1.27E−07 NM_001028.2 IOH5471ribosomal protein S25 (RPS25) AD 1.27E−07 NM_003512.3 IOH14485 HistoneH2A type 1-C AD 1.78E−07 NM_002095.1 IOH22963 general transcriptionfactor IIE, AD 1.97E−07 polypeptide 2, beta 34 kDa (GTF2E2) NM_005720.1IOH3992 actin related protein 2/3 complex, AD 1.97E−07 subunit 1B, 41kDa (ARPC1B) NM_003868.1 IOH42157 fibroblast growth factor 16 AD1.97E−07 (FGF16) NM_004214.3 IOH2103 fibroblast growth factor (acidic)AD 1.97E−07 intracellular binding protein (FIBP), transcript variant 2NM_021079.2 IOH14141 N-myristoyltransferase 1 (NMT1) AD 1.99E−07NM_015833.1 IOH38242 adenosine deaminase, RNA- AD 2.62E−07 specific, B1(RED1 homolog rat) (ADARB1), transcript variant 2 PHR5001 Recombinanthuman CTLA-4/Fc AD 2.62E−07 BC030983.1 IOH23183 immunoglobulin lambdalocus AD 2.62E−07 (IGL@) BC030984.1 IOH23182 cDNA clone MGC: 32654 AD2.62E−07 IMAGE: 4701898, complete cds BC002733.2 IOH5365 chromosome 1open reading frame Control 2.62E−07 77 (C1orf77) NM_133494.1 IOH45126NIMA (never in mitosis gene a)- AD 2.65E−07 related kinase 7 (NEK7)BC010467.1 IOH11119 cDNA clone MGC: 17410 AD 3.42E−07 IMAGE: 4156035,complete cds NM_014060.1 IOH4208 malignant T cell amplified AD 3.42E−07sequence 1 (MCTS1) NM_016167.3 IOH40609 nucleolar protein 7, 27 kDa AD3.81E−07 (NOL7) BC015833.1 IOH14840 cDNA clone MGC: 27152 AD 4.30E−07IMAGE: 4691630, complete cds NM_145063.1 IOH13839 chromosome 6 openreading frame AD 5.08E−07 130 (C6orf130) BC040106.1 IOH26285hypothetical protein HSPC111 AD 5.08E−07 (HSPC111) BC010947.1 IOH14455signal recognition particle 19 kDa AD 5.08E−07 (SRP19) NM_014065.2IOH43942 Protein asteroid homolog 1 AD 5.31E−07 BC012760.2 IOH62834Glycogen synthase kinase-3 beta AD 5.38E−07 NM_004088.1 IOH11297deoxynucleotidyltransferase, AD 6.41E−07 terminal (DNTT), transcriptvariant 1 BC019337.1 IOH12297 immunoglobulin heavy constant AD 7.15E−07gamma 1 (G1m marker) (IGHG1) NM_024316.1 IOH12150 leukocyte receptorcluster (LRC) Control 7.80E−07 member 1 (LENG1) NM_002938.2 IOH41414ring finger protein 4 (RNF4) AD 7.80E−07 NM_006620.2 IOH4029 HBS1-like(S. cerevisiae) AD 8.79E−07 (HBS1L) NM_000992.2 IOH1702 60S ribosomalprotein L29 AD 1.05E−06 NM_024668.2 IOH46162 ankyrin repeat and KHdomain AD 1.05E−06 containing 1 (ANKHD1), transcript variant 3NM_031445.1 IOH5185 AMME chromosomal region gene AD 1.26E−06 1-like(AMMECR1L) NM_003517.2 IOH29296 histone cluster 2, H2ac AD 1.38E−06(HIST2H2AC) BC072419.1 IOH62555 Ig gamma-1 chain C region AD 1.50E−06NM_145174.1 IOH44767 DnaJ (Hsp40) homolog, subfamily AD 1.57E−06 B,member 7 (DNAJB7) BC022361.1 IOH14170 rRNA-processing protein FCF1 AD1.57E−06 homolog BC006376.1 IOH6481 N-myristoyltransferase 2 (NMT2) AD1.60E−06 NM_001895.1 casein kinase 2, alpha 1 AD 1.60E−06 polypeptide(CSNK2A1), transcript variant 2 NM_003524.2 IOH58715 Histone H2B type1-H AD 1.69E−06 BC027951.1 IOH11889 Cas scaffolding protein family AD1.93E−06 member 4 NM_134427.1 IOH45474 regulator of G-protein signaling3 AD 2.02E−06 (RGS3), transcript variant 4 NM_052969.1 IOH12514ribosomal protein L39-like AD 2.02E−06 (RPL39L) NM_023080.1 IOH13369chromosome 8 open reading frame AD 2.17E−06 33 (C8orf33) NM_138779.1IOH10711 chromosome 13 open reading AD 2.17E−06 frame 27 (C13orf27)BC026030.1 IOH14611 zinc finger protein 239 (ZNF239) AD 2.32E−06BC029760.1 IOH22119 OTU domain containing 6B AD 2.76E−06 (OTUD6B)PHC1475 C-C motif chemokine 21 AD 3.00E−06 NM_133336.1 IOH42549Wolf-Hirschhorn syndrome AD 3.44E−06 candidate 1 (WHSC1), transcriptvariant 9 BC034142.1 IOH23177 immunoglobulin kappa variable 1- AD3.67E−06 5 (IGKV1-5) NM_020235.2 IOH44025 bobby sox homolog (Drosophila)AD 3.67E−06 (BBX) NM_198829.1 IOH58974 Ras-related C3 botulinum toxin AD3.89E−06 substrate 1 BC098112.1 IOH63324 Histone H2B type 1-N AD3.89E−06 NM_032359.1 IOH5762 chromosome 3 open reading frame AD 4.32E−0626 (C3orf26) NM_001966.2 IOH62346 Peroxisomal bifunctional enzyme AD4.32E−06 BC032451.1 IOH21663 cDNA clone MGC: 40426 AD 4.76E−06 IMAGE:5178085, complete cds XM_379117.1 IOH43619 PREDICTED: Homo sapiens AD4.98E−06 hypothetical protein LOC150568 (LOC150568) BC033159.1 IOH23223DnaJ (Hsp40) homolog, subfamily AD 4.98E−06 C, member 8 (DNAJC8)NM_006756.2 IOH42106 transcription elongation factor A AD 4.98E−06(SII), 1 (TCEA1), transcript variant 1 NM_016940.1 IOH12821 RWD domaincontaining 2B AD 5.00E−06 (RWDD2B) NM_177559.2 IOH13704 casein kinase 2,alpha 1 AD 5.00E−06 polypeptide (CSNK2A1), transcript variant 1NM_004178.3 IOH45867 TAR (HIV-1) RNA binding AD 5.13E−06 protein 2(TARBP2), transcript variant 3 NM_032338.2 IOH7537 chromosome 12 openreading AD 5.22E−06 frame 31 (C12orf31) BC005955.1 IOH7485 chromosome 8open reading frame AD 5.50E−06 53 (C8orf53) NM_001009613.1 IOH58584Sperm protein associated with the AD 5.50E−06 nucleus on the Xchromosome N4 BC036723.1 IOH22599 Fc fragment of IgG, low affinity AD5.50E−06 IIIa, receptor (CD16a) (FCGR3A) NM_003690.3 IOH57108Interferon-inducible double AD 6.84E−06 stranded RNA-dependent proteinkinase activator A NM_014473.2 IOH9851 DIM1 dimethyladenosine AD6.91E−06 transferase 1-like (S. cerevisiae) (DIMT1L) NM_032855.1IOH14623 hematopoietic SH2 domain AD 7.69E−06 containing (HSH2D)NM_001167.2 IOH21984 baculoviral IAP repeat-containing AD 7.69E−06 4(BIRC4) NM_178571.2 IOH26524 hypothetical protein MGC51025 AD 7.69E−06(MGC51025) NM_003600.1 aurora kinase A (AURKA), AD 7.69E−06 transcriptvariant 2 NM_006912.3 IOH29584 Ras-like without CAAX 1 (RIT1) AD8.05E−06 NM_005307.1 G protein-coupled receptor kinase 4 AD 8.29E−06BC001280.1 IOH21165 Serine/threonine-protein kinase 6 AD 8.71E−06NM_182970.2 IOH43687 regulating synaptic membrane AD 8.71E−06 exocytosis4 (RIMS4) NM_153332.2 IOH27323 three prime histone mRNA AD 8.71E−06exonuclease 1 (THEX1) NM_139016.2 IOH27635 chromosome 20 open reading AD8.88E−06 frame 198 (C20orf198) NM_003677.3 IOH56971 Density-regulatedprotein AD 1.15E−05 NM_013293.1 IOH9999 Transformer-2 protein homolog AD1.15E−05 NM_014481.2 IOH4887 APEX nuclease Control 1.17E−05(apurinic/apyrimidinic endonuclease) 2 (APEX2), nuclear gene encodingmitochondrial protein BC033856.1 IOH21797 La ribonucleoprotein domain AD1.18E−05 family, member 1 (LARP1) NM_000939.1 IOH40048proopiomelanocortin AD 1.18E−05 (adrenocorticotropin/beta-lipotropin/alpha-melanocyte stimulating hormone/beta- melanocytestimulating hormone/ beta-endorphin) (POMC), transcript variant 2BC009348.2 IOH12064 cirrhosis, autosomal recessive 1A AD 1.29E−05(cirhin) (CIRH1A) NM_014508.2 IOH54737 apolipoprotein B mRNA editing AD1.46E−05 enzyme, catalytic polypeptide-like 3C (APOBEC3C), mRNA.NM_080659.1 IOH7410 chromosome 11 open reading AD 1.48E−05 frame 52(C11orf52) NM_022755.2 IOH10937 inositol 1,3,4,5,6- AD 1.54E−05pentakisphosphate 2-kinase (IPPK) NM_002690.1 IOH41443 polymerase (DNAdirected), beta AD 1.57E−05 (POLB) BC011668.1 Casein kinase II subunitalpha AD 1.57E−05 NM_002128.2 IOH2937 high-mobility group box 1 AD1.62E−05 (HMGB1) BC012472.1 IOH11069 ubiquitin D (UBD) AD 1.62E−05BC030020.2 IOH22410 DEAD (Asp-Glu-Ala-Asp) box AD 1.62E−05 polypeptide55 (DDX55) BC018060.1 IOH11303 Ras-like without CAAX 2 (RIT2) AD1.62E−05 NM_003141.2 IOH9948 tripartite motif-containing 21 AD 1.62E−05(TRIM21) NM_007054.1 IOH26900 kinesin family member 3A AD 1.62E−05(KIF3A) NM_006924.3 IOH11039 splicing factor, arginine/serine- AD1.67E−05 rich 1 (splicing factor 2, alternate splicing factor) (SFRS1),transcript variant 1 NM_032563.1 IOH40397 late cornified envelope 3D AD1.67E−05 (LCE3D) NM_173080.1 IOH34934 small proline-rich protein 4 AD1.67E−05 (SPRR4) NM_003527.4 IOH58710 Histone H2B type 1-O AD 1.82E−05BC009762.2 IOH14113 Tripartite motif-containing protein AD 1.82E−05 41NM_006861.2 IOH10011 RAB35, member RAS oncogene AD 1.83E−05 family(RAB35) NM_002136.1 IOH3526 heterogeneous nuclear AD 1.90E−05ribonucleoprotein A1 (HNRNPA1), transcript variant 1 BC009623.1 IOH9844nucleophosmin (nucleolar AD 2.11E−05 phosphoprotein B23, numatrin)(NPM1) NM_021063.2 IOH58956 Histone H2B type 1-D AD 2.11E−05 BC054021.1IOH29457 pterin-4 alpha-carbinolamine AD 2.29E−05dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha(TCF1) 2 (PCBD2) NM_012108.1 IOH13463 signal transducing adaptor familyAD 2.63E−05 member 1 (STAP1) NM_023937.1 IOH4594 mitochondrial ribosomalprotein AD 3.15E−05 L34 (MRPL34), nuclear gene encoding mitochondrialprotein XM_088679.2 IOH43003 Spermatid nuclear transition AD 3.33E−05protein 4 NM_022720.5 IOH52788 DiGeorge syndrome critical region AD3.33E−05 gene 8 (DGCR8) NM_016073.2 IOH10649 hepatoma-derived growthfactor, AD 3.33E−05 related protein 3 (HDGFRP3) NM_018105.1 IOH10776THAP domain containing, AD 3.41E−05 apoptosis associated protein 1(THAP1), transcript variant 1 NM_005371.2 IOH4172 methyltransferase like1 AD 3.56E−05 (METTL1), transcript variant 1 BC029427.1 IOH23192coiled-coil domain containing 23 AD 3.61E−05 (CCDC23) NM_032476.1IOH13845 mitochondrial ribosomal protein AD 3.66E−05 S6 (MRPS6), nucleargene encoding mitochondrial protein NM_014110.3 IOH39485 proteinphosphatase 1, regulatory Control 3.66E−05 (inhibitor) subunit 8(PPP1R8), transcript variant 1 NM_003089.4 IOH40192 small nuclearribonucleoprotein AD 3.88E−05 70 kDa polypeptide (RNP antigen) (SNRP70)BC020972.1 Casein kinase I isoform gamma-2 AD 3.88E−05 BC000381.2IOH3454 TBP-like 1 (TBPL1) AD 3.88E−05 NM_007285.5 IOH7450 GABA(A)receptor-associated AD 3.99E−05 protein-like 2 (GABARAPL2) NM_004060.2IOH4393 cyclin G1 (CCNG1), transcript AD 4.02E−05 variant 1 BC001780.1IOH4955 Uncharacterized methyltransferase AD 4.02E−05 WBSCR22NM_022048.1 IOH21026 casein kinase 1, gamma 1 AD 4.02E−05 (CSNK1G1)BC035256.1 IOH27660 Putative adenylate kinase 7 AD 4.19E−05 NM_175887.2IOH27336 proline rich 15 (PRR15) AD 4.22E−05 BC010919.1 IOH27800ribosomal protein L35 (RPL35) AD 4.79E−05 NM_016207.2 IOH14059 cleavageand polyadenylation AD 5.24E−05 specific factor 3, 73 kDa (CPSF3)BC000784.1 IOH4711 baculoviral IAP repeat-containing AD 5.50E−05 5(survivin) (BIRC5) NM_002364.1 IOH11315 melanoma antigen family B, 2 AD5.50E−05 (MAGEB2) NM_022839.2 IOH1783 mitochondrial ribosomal protein AD6.97E−05 S11 (MRPS11), nuclear gene encoding mitochondrial protein,transcript variant 1 NM_014370.2 IOH60262 SFRS protein kinase 3 (SRPK3)AD 6.97E−05 NM_016505.2 IOH6093 zinc finger, CCHC domain AD 7.25E−05containing 17 (ZCCHC17) BC030813.1 IOH23055 cDNA clone MGC: 22645 AD7.42E−05 IMAGE: 4700961, complete cds BC020803.1 IOH14817developmentally regulated GTP AD 7.42E−05 binding protein 1 (DRG1)NM_205848.1 IOH43389 synaptotagmin VI (SYT6) AD 7.94E−05 NM_006398.2IOH59996 Ubiquitin D AD 7.94E−05 NM_017646.3 IOH37769 tRNAisopentenyltransferase 1 AD 8.04E−05 (TRIT1) NM_006925.2 IOH58606Splicing factor, arginine/serine- AD 8.04E−05 rich 5 NM_153822.1IOH41107 proteasome (prosome, macropain) AD 8.43E−05 26S subunit,non-ATPase, 4 (PSMD4), transcript variant 2 NM_014321.2 IOH39827 originrecognition complex, AD 0.000103 subunit 6 like (yeast) (ORC6L)BC012876.1 IOH10177 Ig lambda chain C regions AD 0.000104 NM_021967.1IOH45915 small EDRK-rich factor 1A AD 0.000104 (telomeric) (SERF1A)NM_003295.1 IOH25767 tumor protein, translationally- AD 0.000104controlled 1 (TPT1) NM_017503.2 IOH12519 surfeit 2 (SURF2) AD 0.000105BC018137.1 IOH10369 TATA box binding protein (TBP)- AD 0.000108associated factor, RNA polymerase I, B, 63 kDa (TAF1B) BC005004.1IOH4814 family with sequence similarity AD 0.000114 64, member A(FAM64A) NM_152373.2 IOH14361 zinc finger protein 684 (ZNF684) AD0.000114 NM_000989.2 IOH3809 ribosomal protein L30 (RPL30) AD 0.000121NM_000800.2 IOH21917 fibroblast growth factor 1 (acidic) AD 0.000121(FGF1), transcript variant 1 NM_000975.2 IOH1740 ribosomal protein L11(RPL11) AD 0.000142 BC064144.1 IOH40037 spermatogenesis associated 1Control 0.000142 (SPATA1) PHC1695 C—X—C motif chemokine 11 AD 0.000151NM_022140.2 IOH38016 Band 4.1-like protein 4A AD 0.000159 NM_016287.2IOH43530 heterochromatin protein 1, binding AD 0.000162 protein 3(HP1BP3) BC015586.2 IOH46065 laminin, gamma 1 (formerly AD 0.000162LAMB2) (LAMC1) NM_023931.1 IOH3950 zinc finger protein 747 (ZNF747) AD0.000168 NM_153207.2 IOH14301 AE binding protein 2 (AEBP2) AD 0.000168NM_007079.2 IOH4497 Protein tyrosine phosphatase type AD 0.000168 IVA 3NM_004397.3 IOH45655 Probable ATP-dependent RNA AD 0.000172 helicaseDDX6 NM_012424.2 Ribosomal protein S6 kinase AD 0.000172 delta-1CCP_1BSA NA Control 0.000177 NM_020239.2 IOH21482 CDC42 small effector 1AD 0.000186 (CDC42SE1), transcript variant 2 BC029378.1 IOH23186telomeric repeat binding factor AD 0.000186 (NIMA-interacting) 1 (TERF1)BC062732.1 IOH62856 Ig kappa chain C region Control 0.000211 BC000306.1IOH3456 hydroxyacyl-Coenzyme A AD 0.000216 dehydrogenase (HADH)BC031650.1 IOH22742 Putative E3 ubiquitin-protein Control 0.000221ligase SH3RF2 NM_182692.1 IOH38187 Serine/threonine-protein kinase AD0.000227 SRPK2 NM_032350.3 IOH6347 Uncharacterized protein C7orf50 AD0.000227 NM_001022.3 IOH4572 ribosomal protein S19 (RPS19) AD 0.000227NM_001002913.1 IOH26561 peptidyl-tRNA hydrolase 1 AD 0.000227 homolog(S. cerevisiae) (PTRH1) BC000535.1 IOH4145 Suppressor of SWI4 1 homologAD 0.000227 NM_017692.1 IOH4894 aprataxin (APTX), transcript AD 0.000233variant 4 NM_000993.2 IOH14051 ribosomal protein L31 (RPL31), AD0.000245 transcript variant 1 NM_152653.1 IOH13176 ubiquitin-conjugatingenzyme E2E AD 0.000245 2 (UBC4/5 homolog, yeast) (UBE2E2) NM_014891.1IOH4282 PDGFA associated protein 1 AD 0.000245 (PDAP1) NM_012148.1IOH39321 double homeobox, 3 (DUX3) AD 0.000252 NM_024046.1 CaMkinase-like vesicle- AD 0.00028 associated (CAMKV) NM_022063.1 IOH27864chromosome 10 open reading AD 0.00028 frame 84 (C10orf84) BC036434.1IOH62212 Serine/threonine-protein kinase AD 0.00032 VRK2 NM_001396.2Dual specificity tyrosine- AD 0.00032 phosphorylation-regulated kinase1A NM_004939.1 IOH14578 DEAD (Asp-Glu-Ala-Asp) box AD 0.00032polypeptide 1 (DDX1) NM_001039724.1 IOH63165 Nostrin AD 0.000331NM_138551.1 IOH13700 thymic stromal lymphopoietin AD 0.000332 (TSLP),transcript variant 2 XM_379194.1 IOH43490 PREDICTED: Homo sapiens AD0.000332 hypothetical LOC401068 (LOC401068) BC007401.2 IOH5852 celldivision cycle 25 homolog A AD 0.00034 (S. pombe) (CDC25A) BC008902.2IOH46064 GRIP and coiled-coil domain- AD 0.00034 containing protein 1BC019039.2 IOH46089 Regulator of G-protein signaling 3 AD 0.000407NM_016050.1 IOH4903 mitochondrial ribosomal protein AD 0.000432 L11(MRPL11), nuclear gene encoding mitochondrial protein, transcriptvariant 1 NM_002927.3 IOH11040 regulator of G-protein signaling 13 AD0.000432 (RGS13), transcript variant 1 NM_207430.1 IOH59509 FLJ46266protein (FLJ46266), AD 0.000432 mRNA. NM_016508.2 IOH21339Cyclin-dependent kinase-like 3 AD 0.000432 NM_197964.1 IOH7576chromosome 7 open reading frame AD 0.000442 55 (C7orf55) BC021930.1IOH13703 KIAA1530 protein (KIAA1530) AD 0.000442 NM_145043.1 IOH13260nei like 2 (E. coli) (NEIL2) AD 0.000442 BC030586.2 IOH22241 signaltransducing adaptor AD 0.000442 molecule (SH3 domain and ITAM motif) 1(STAM) BC004292.1 IOH22899 PHD finger protein 15 (PHF15) Control0.000442 BC022378.1 IOH13502 zinc finger with KRAB and SCAN AD 0.000443domains 1 (ZKSCAN1) NM_003792.1 IOH10852 endothelialdifferentiation-related AD 0.000448 factor 1 (EDF1), transcript variantalpha BC070154.1 IOH63011 Non-histone chromosomal protein AD 0.000448HMG-14 BC010074.2 IOH13694 FUS interacting protein AD 0.000479(serine/arginine-rich) 1 (FUSIP1) NM_002201.3 IOH6793 interferonstimulated exonuclease AD 0.000479 gene 20 kDa (ISG20) BC033621.2IOH21688 Pseudouridylate synthase 7 AD 0.000481 homolog-like proteinNM_004114.2 IOH13832 fibroblast growth factor 13 AD 0.00054 (FGF13),transcript variant 1A NM_016483.3 IOH22255 PHD finger protein 7 (PHF7),AD 0.00054 transcript variant 1 NM_012420.1 IOH22625 interferon-inducedprotein with AD 0.000543 tetratricopeptide repeats 5 (IFIT5) NM_016203.2IOH42382 protein kinase, AMP-activated, AD 0.000543 gamma 2non-catalytic subunit (PRKAG2), transcript variant a, mRNA. NM_014878.2IOH10030 Pumilio domain-containing AD 0.000544 protein KIAA0020NM_018664.1 IOH44746 Jun dimerization protein p21SNFT AD 0.000593 (SNFT)NM_002402.1 IOH3706 mesoderm specific transcript AD 0.000613 homolog(mouse) (MEST), transcript variant 1 NM_003769.2 IOH41184 splicingfactor, arginine/serine- AD 0.000613 rich 9 (SFRS9) NM_018132.3 IOH45979centromere protein Q (CENPQ) AD 0.000613 NM_006072.4 IOH40395 chemokine(C-C motif) ligand 26 AD 0.000613 (CCL26) NM_021029.3 IOH4423 ribosomalprotein L36a (RPL36A) AD 0.000638 NM_000978.2 IOH13951 ribosomal proteinL23 (RPL23) AD 0.000638 NM_001023.2 IOH6083 ribosomal protein S20(RPS20) AD 0.000638 BC013366.2 IOH27815 UNC-112 related protein 2 AD0.000638 (URP2) BC001327.1 IOH3125 interferon-related developmental AD0.000644 regulator 2 (IFRD2) BC000522.1 IOH3622 serpin peptidaseinhibitor, clade F AD 0.000644 (alpha-2 antiplasmin, pigment epitheliumderived factor), member 1 (SERPINF1) NM_019067.1 IOH13693 guaninenucleotide binding AD 0.000644 protein-like 3 (nucleolar)-like (GNL3L)NM_152634.1 IOH21490 TFS2-M domain-containing AD 0.000644 protein 1(MGC17403) BC011842.2 IOH14099 hypothetical protein FLJ11184 AD 0.00065(FLJ11184) BC068514.1 IOH40543 NF-kappaB repressing factor AD 0.00065(NKRF) NM_018063.3 IOH44165 helicase, lymphoid-specific AD 0.000661(HELLS) NM_198467.1 IOH40427 round spermatid basic protein 1- AD0.000739 like (RSBN1L) NM_198517.2 IOH25922 TBC1 domain family, memberAD 0.000835 10C (TBC1D10C) NM_001564.1 IOH22913 inhibitor of growthfamily, AD 0.000835 member 2 (ING2) NM_002930.1 IOH54792 GTP-bindingprotein Rit2 AD 0.000835 NM_019058.1 IOH6497 DNA-damage-inducibletranscript AD 0.000835 4 protein NM_020661.1 IOH6382 activation-inducedcytidine AD 0.000868 deaminase (AICDA) NM_144659.1 IOH21795 t-complex 10(mouse)-like Control 0.000868 (TCP10L) NM_173822.1 IOH27491 family withsequence similarity AD 0.000898 126, member B (FAM126B) BC056887.1IOH29097 chromosome 5 open reading frame AD 0.000898 5 (C5orf5)BC070334.1 IOH40810 immunoglobulin kappa constant AD 0.000898 (IGKC)NM_004071.1 Dual specificity protein kinase AD 0.000898 CLK1 XM_378514.1IOH42688 PREDICTED: Homo sapiens Control 0.000901 hypothetical proteinLOC283663 (LOC283663), mRNA NM_005801.2 IOH6916 eukaryotic translationinitiation AD 0.000906 factor 1 (EIF1) BC001487.2 IOH12155 TARDNA-binding protein 43 AD 0.000906 NM_006790.1 IOH7249 myotilin (MYOT)AD 0.000906 NM_175923.2 IOH22051 hypothetical protein MGC42630 AD0.000906 (MGC42630) NM_000122.1 IOH6320 excision repair cross- AD0.000918 complementing rodent repair deficiency, complementation group 3(xeroderma pigmentosum group B complementing) (ERCC3) NM_001819.1IOH3444 chromogranin B (secretogranin 1) Control 0.000992 (CHGB)BC010501.1 IOH10253 Catenin delta-1 AD 0.001011 BC005298.1 IOH7271cyclin-dependent kinase 7 (MO15 AD 0.001015 homolog, Xenopus laevis,cdk- activating kinase) (CDK7) PHC0076 interleukin 7 (IL7) AD 0.001041NM_138349.2 IOH45741 Tumor protein p53-inducible AD 0.001041 protein 13BC000044.1 IOH4604 Spindlin-2B AD 0.001041 NM_014747.2 IOH4568regulating synaptic membrane AD 0.001117 exocytosis 3 (RIMS3)NM_001014.2 IOH4063 ribosomal protein S10 (RPS10) AD 0.001122NM_005678.3 IOH45840 SNRPN upstream reading frame AD 0.001122 (SNURF),transcript variant 1 BC010876.1 IOH9862 nei endonuclease VIII-like 1 (E.coli) AD 0.001122 (NEIL1) BC025281.1 IOH14071 RNA binding motif protein9 AD 0.001147 (RBM9) NM_001013.2 IOH5840 ribosomal protein S9 (RPS9) AD0.001147 NM_015414.2 IOH4985 ribosomal protein L36 (RPL36), AD 0.001201transcript variant 2 NM_017566.2 IOH11408 kelch domain containing 4 AD0.001209 (KLHDC4) BC015818.1 IOH14254 lectin, galactoside-binding, AD0.001262 soluble, 8 (galectin 8) (LGALS8) BC036109.1 IOH27253 SECISbinding protein 2 AD 0.001265 (SECISBP2) NM_005738.1 IOH5077ADP-ribosylation factor-like 4A AD 0.001498 (ARL4A), transcript variant1 BC022816.1 IOH14672 NA AD 0.001498 NM_024303.1 IOH5245 zinc finger andSCAN domain AD 0.001533 containing 5 (ZSCAN5) BC018823.2 IOH14860splicing factor, arginine/serine- AD 0.001533 rich 5 (SFRS5) NM_024319.1IOH5397 chromosome 1 open reading frame AD 0.001533 35 (C1orf35) PV3359Ephrin receptor A3 (EPHA3), AD 0.00166 transcript variant 1 BC006318.1IOH6433 erythrocyte membrane protein Control 0.001674 band 4.9 (dematin)(EPB49) NM_145899.1 IOH6516 high mobility group AT-hook 1 AD 0.001732(HMGA1), transcript variant 1 NM_021158.1 tribbles homolog 3(Drosophila) AD 0.001796 (TRIB3) NM_005794.2 IOH41302dehydrogenase/reductase (SDR AD 0.001796 family) member 2 (DHRS2),transcript variant 2 BC005807.2 IOH6261 stearoyl-CoA desaturase(delta-9- AD 0.001796 desaturase) (SCD) NM_006374.2 IOH6735serine/threonine kinase 25 (STE20 AD 0.001796 homolog, yeast) (STK25)NM_152757.1 IOH43336 Putative uncharacterized protein AD 0.001796C20orf200 NM_001009880.1 IOH42078 chromosome 22 open reading AD 0.001796frame 9 (C22orf9), transcript variant 2 NM_138558.1 IOH13759 proteinphosphatase 1, regulatory AD 0.001796 (inhibitor) subunit 8 (PPP1R8),transcript variant 2 BC007852.1 Serine/threonine-protein kinase 25 AD0.001796 NM_012396.1 IOH12626 pleckstrin homology-like domain, AD0.001845 family A, member 3 (PHLDA3) NM_012437.2 IOH3724 SNAP-associatedprotein AD 0.001845 (SNAPAP) PHC0205 interleukin 20 (IL20) AD 0.001845NM_016093.2 IOH14674 ribosomal protein L26-like 1 AD 0.001845 (RPL26L1)NM_005902.1 IOH27044 SMAD family member 3 AD 0.001845 (SMAD3)XM_375456.2 IOH43380 Ataxin-7-like protein 3 AD 0.001925 NM_006275.2IOH3168 splicing factor, arginine/serine- AD 0.00196 rich 6 (SFRS6)NM_018037.1 IOH45458 Ral GEF with PH domain and Control 0.001993 SH3binding motif 2 (RALGPS2), transcript variant 1 BC011600.1 IOH13680 cDNAclone IMAGE: 3050953, AD 0.002095 **** WARNING: chimeric clone ****NM_014570.2 IOH5693 ADP-ribosylation factor GTPase AD 0.002095activating protein 3 (ARFGAP3) NM_022551.2 IOH41520 ribosomal proteinS18 (RPS18) AD 0.002095 BC063275.1 IOH40423 eukaryotic translationinitiation AD 0.002095 factor 2C, 1 (EIF2C1) BC062423.1 IOH40739chromosome 7 open reading frame AD 0.0021 41 (C7orf41) NM_170676.2IOH26710 Meis homeobox 2 (MEIS2), Control 0.002174 transcript variant dBC096708.1 IOH63336 Wilms tumor-associated protein AD 0.002181NM_199123.1 IOH42083 SET domain containing 3 AD 0.002181 (SETD3),transcript variant 2 BC010907.1 IOH12088 PAK1 interacting protein 1 AD0.002181 (PAK1IP1) NM_004217.1 aurora kinase B (AURKB) AD 0.002181NM_005737.3 IOH44753 ADP-ribosylation factor-like 4C AD 0.002186 (ARL4C)NM_020467.2 IOH3994 small trans-membrane and AD 0.002186 glycosylatedprotein (LOC57228), transcript variant 2 BC021180.2 IOH11041high-mobility group box 4 AD 0.002209 (HMGB4) NM_004728.2 IOH46173 DEAD(Asp-Glu-Ala-Asp) box AD 0.002209 polypeptide 21 (DDX21) BC030702.1IOH22356 microcephaly, primary autosomal AD 0.002281 recessive 1 (MCPH1)NM_003724.1 IOH26418 jerky homolog (mouse) (JRK), AD 0.002281 transcriptvariant 1 NM_016077.1 IOH3153 peptidyl-tRNA hydrolase 2 AD 0.002329(PTRH2), nuclear gene encoding mitochondrial protein BC022362.1 IOH14191cDNA clone MGC: 23888 Control 0.002364 IMAGE: 4704496, complete cdsNM_014955.2 IOH45543 KIAA0859 (KIAA0859), AD 0.002364 transcript variant2 NM_001834.2 IOH43456 clathrin, light chain (Lcb) (CLTB), Control0.002495 transcript variant 1, mRNA. NM_002045.1 IOH6708 growthassociated protein 43 Control 0.002495 (GAP43) NM_003503.2 Cell divisioncycle 7-related AD 0.00252 protein kinase NM_022491.2 IOH62643 Sin3histone deacetylase Control 0.002538 corepressor complex component SDS3NM_004987.3 IOH55033 LIM and senescent cell antigen- Control 0.002538like-containing domain protein 1 BC017212.2 IOH13041 PHD finger protein11 (PHF11) AD 0.0027 NM_019069.3 IOH26403 WD repeat domain 5B (WDR5B) AD0.00274 BC094719.1 IOH62673 Rho GTPase-activating protein 12 AD 0.002753BC021187.1 IOH10893 DKFZP434K028 protein AD 0.00278 (DKFZP434K028)NM_003948.2 Cyclin-dependent kinase-like 2 AD 0.00278 BC040183.2IOH27627 Rap guanine nucleotide exchange AD 0.00278 factor (GEF) 4(RAPGEF4) NM_014061.3 IOH10824 melanoma antigen family H, 1 AD 0.00278(MAGEH1) BC032587.1 IOH21953 tubby like protein 3 (TULP3) AD 0.002953BC005332.1 IOH7177 cDNA clone MGC: 12418 AD 0.003171 IMAGE: 3934658,complete cds BC033710.2 IOH45968 RAD54 homolog B (S. cerevisiae) AD0.003171 (RAD54B) BC010425.1 IOH27813 acyl-Coenzyme A oxidase 1, AD0.003171 palmitoyl (ACOX1) NM_021138.2 IOH21846 TNF receptor-associatedfactor 2 AD 0.003171 (TRAF2) BC093990.1 IOH62017 Sin3 histonedeacetylase AD 0.003185 corepressor complex component SDS3 NM_014288.2IOH13691 Centromere protein R AD 0.003283 NM_024826.1 IOH42194Microtubule-associated protein 9 AD 0.003283 BC035968.1 IOH27970chloride intracellular channel 5 AD 0.003283 (CLIC5) BC096165.1 IOH59027Troponin I, cardiac muscle AD 0.003432 BC012105.1 IOH14609 nuclearVCP-like (NVL) AD 0.003548 BC011924.1 IOH12682 unkempt homolog(Drosophila)- AD 0.003548 like (UNKL) NM_001311.2 IOH5361 Cysteine-richprotein 1 AD 0.003548 NM_014445.2 IOH41298 stress-associated endoplasmicAD 0.003548 reticulum protein 1 (SERP1) NM_005979.1 IOH1589 S100 calciumbinding protein A13 AD 0.003548 (S100A13), transcript variant 2BC036923.1 IOH25928 chromosome 9 open reading frame AD 0.003733 150(C9orf150) NM_033671.1 IOH43039 cyclin B3 (CCNB3), transcript AD0.003733 variant 2 NM_201998.1 IOH56887 Splicing factor 1 Control0.003827 BC014441.1 IOH13328 NOL1/NOP2/Sun domain family, AD 0.003841member 4 (NSUN4) BC031549.1 IOH21007 CDC-like kinase 1 (CLK1) AD0.003841 NM_194290.1 IOH42276 cDNA FLJ42001 fis, clone AD 0.003841SPLEN2029912 (LOC153684 protein) [Source: UniProtKB/TrEMBL; Acc: Q6ZVW3]BC053984.1 IOH29361 immunoglobulin heavy variable 4- AD 0.003841 31(IGHV4-31) BC050563.1 IOH26951 hypothetical protein LOC202051 AD0.003841 (LOC202051) BC050718.1 IOH27017 polymerase (DNA directed) kappaAD 0.00385 (POLK) BC000896.1 IOH3226 RAB10, member RAS oncogene AD0.00385 family (RAB10) NM_006252.2 IOH29876 AMP-activated protein_kinaseAD 0.00385 A2/B1/G1: PRKAA2/B1/G1 sequences are seperated by - (inprotein list file). BC013630.1 IOH10193 JTV1 gene (JTV1) AD 0.00385BC009108.1 IOH10191 cDNA clone IMAGE: 3451214 AD 0.003975 (MCM10)BC002645.1 IOH5243 syntaxin 5 (STX5) AD 0.003975 NM_138414.1 IOH10524coiled-coil domain containing 101 AD 0.004133 (CCDC101) NM_002740.1protein kinase C, iota (PRKCI) AD 0.004133 NM_002822.3 IOH40883twinfilin, actin-binding protein, AD 0.004234 homolog 1 (Drosophila)(TWF1) BC003566.1 IOH4871 zinc finger protein 24 (ZNF24) AD 0.004412NM_022756.2 IOH13235 Uncharacterized protein C1orf149 AD 0.004679NM_153035.1 IOH27410 chromosome 1 open reading frame AD 0.004754 83(C1orf83) NM_177524.1 IOH45900 mesoderm specific transcript AD 0.004766homolog (mouse) (MEST), transcript variant 2 NM_004635.2 IOH3889mitogen-activated protein kinase- AD 0.004766 activated protein kinase 3(MAPKAPK3) NM_005607.1 Focal adhesion kinase 1 AD 0.004766 BC010697.1IOH9799 RNA-binding protein 40 AD 0.004766 NM_174942.1 IOH26291GAS2-like protein 3 AD 0.004766 BC038976.1 IOH28763 RhoGTPase-activating protein 15 AD 0.004867 NM_012117.1 IOH3162 chromoboxhomolog 5 (HP1 alpha AD 0.004867 homolog, Drosophila) (CBX5) NM_013313.3IOH43282 yippee-like 1 (Drosophila) AD 0.005052 (YPEL1) NM_148179.1IOH23094 chromosome 9 open reading frame AD 0.0051 23 (C9orf23),transcript variant 2 BC038105.2 IOH27173 membrane protein, palmitoylatedAD 0.0051 7 (MAGUK p55 subfamily member 7) (MPP7) BC091489.1 IOH62570zinc finger, MYND domain AD 0.0051 containing 11, mRNA (cDNA clone MGC:111056 IMAGE: 6186814), complete cds BC034435.1 IOH21500 zinc fingerCCCH-type containing AD 0.0051 3 (ZC3H3) NM_152736.2 IOH14153 Zincfinger protein 187 AD 0.0051 NM_015014.1 IOH23193 RNA binding motifprotein 34 AD 0.005622 (RBM34) NM_003137.2 SFRS protein kinase 1 (SRPK1)AD 0.005622 BC016486.1 IOH21471 lectin, galactoside-binding, AD 0.005695soluble, 8 (galectin 8) (LGALS8) BC000238.1 IOH4394 ankyrin repeat andzinc finger AD 0.005695 domain containing 1 (ANKZF1) NM_002904.4IOH14621 RD RNA binding protein (RDBP) AD 0.005695 BC009046.1 IOH3394neurogenic differentiation 1 AD 0.005695 (NEUROD1) NM_198965.1 IOH44500Parathyroid hormone-related AD 0.005695 protein BC047776.2 IOH26688coiled-coil domain containing 43 AD 0.005695 (CCDC43) BC002914.1 IOH5733WAS/WASL-interacting protein Control 0.005832 family member 1NM_001004306.1 IOH40085 similar to hypothetical protein AD 0.005898FLJ36492 (MGC87631) NM_006800.2 IOH45528 male-specific lethal 3-like 1AD 0.005898 (Drosophila) (MSL3L1), transcript variant 3 NM_006038.1IOH14383 spermatogenesis associated 2 AD 0.005898 (SPATA2) NM_014477.2IOH22106 chromosome 20 open reading AD 0.005898 frame 10 (C20orf10)BC027612.2 IOH11844 EP300-interacting inhibitor of AD 0.005898differentiation 3 NM_017411.2 IOH10903 survival of motor neuron 2, AD0.005898 centromeric (SMN2), transcript variant d BC004876.1 IOH5626Protein MCM10 homolog AD 0.005898 NM_201516.1 IOH45833 H2A histonefamily, member V AD 0.005917 (H2AFV), transcript variant 4 NM_199290.2IOH40757 Nascent polypeptide-associated Control 0.006165 complex subunitalpha-2 BC006273.1 IOH6379 T-cell activation NFKB-like Control 0.006165protein (TA-NFKBH) NM_014012.2 IOH26198 RAS (RAD and GEM)-like GTP-Control 0.006165 binding 1 (REM1) BC012499.1 IOH11855 NAD-dependentdeacetylase Control 0.006165 sirtuin-1 NM_022156.3 IOH39856dihydrouridine synthase 1-like (S. cerevisiae) AD 0.006165 (DUS1L)BC015742.1 IOH12050 polymerase (DNA directed), eta AD 0.006497 (POLH)NM_001015509.1 IOH54713 Peptidyl-tRNA hydrolase 2, AD 0.006497mitochondrial NM_014366.1 IOH4189 guanine nucleotide binding AD 0.006531protein-like 3 (nucleolar) (GNL3), transcript variant 1 NM_018357.2IOH6558 La ribonucleoprotein domain AD 0.006544 family, member 6(LARP6), transcript variant 1 BC020221.1 IOH13291 SH3 and cysteine richdomain AD 0.006912 (STAC) NM_005307.1 G protein-coupled receptor kinase4 AD 0.006912 NM_017785.2 IOH12118 coiled-coil domain containing 99 AD0.006926 (CCDC99) BC026101.2 IOH10652 nudE nuclear distribution gene EAD 0.006926 homolog (A. nidulans)-like 1 (NDEL1) NM_175571.2 IOH44212GTPase, IMAP family member 8 AD 0.006926 (GIMAP8) NM_004286.2 IOH14552GTP binding protein 1 (GTPBP1) AD 0.006926 BC072461.1 IOH62565 Cysteineand histidine-rich AD 0.006926 domain-containing protein 1 BC047945.1IOH26362 tripartite motif-containing 69 AD 0.006926 (TRIM69) BC005858.1IOH5967 fibronectin 1 (FN1) AD 0.006926 NM_001722.2 IOH4103 polymerase(RNA) III (DNA AD 0.006926 directed) polypeptide D, 44 kDa (POLR3D)NM_024333.1 IOH4546 Fibronectin type III and SPRY AD 0.006926domain-containing protein 1 NM_144595.1 IOH25832 SLAIN motif family,member 1 AD 0.006926 (SLAIN1), transcript variant 2 NM_002469.1 IOH13806myogenic factor 6 (herculin) AD 0.006926 (MYF6) BC053866.1 IOH28947endothelin 3 (EDN3) AD 0.006926 NM_001319.5 IOH10417 casein kinase 1,gamma 2 AD 0.006926 (CSNK1G2) BC006124.1 IOH6586 IMP (inosinemonophosphate) AD 0.006926 dehydrogenase 2 (IMPDH2) NM_014667.1 IOH29305vestigial like 4 (Drosophila) AD 0.006926 (VGLL4) NM_031465.2 IOH6623chromosome 12 open reading AD 0.006926 frame 32 (C12orf32) NM_182612.1IOH42453 Parkinson disease 7 domain AD 0.006926 containing 1 (PDDC1)PV4803 epidermal growth factor receptor AD 0.006926 (erythroblasticleukemia viral (v- erb-b) oncogene homolog, avian) (EGFR); see catalognumber for detailed information on wild-type or point mutant statusNM_152266.1 IOH13579 chromosome 19 open reading AD 0.006926 frame 40(C19orf40) NM_000997.2 IOH1585 ribosomal protein L37 (RPL37) AD 0.00699BC001728.1 IOH4430 TCF3 fusion partner AD 0.00699 BC007015.1 IOH29312cyclin E2 (CCNE2) AD 0.00699 NM_022347.1 IOH41552 interferon responsivegene 15 AD 0.00699 (IFRG15) BC031821.1 IOH22188 Secernin-3 AD 0.007845NM_016304.2 IOH7552 chromosome 15 open reading AD 0.007845 frame 15(C15orf15) BC069677.1 IOH61907 Regulator of G-protein signaling 8 AD0.008076 BC013331.1 IOH13858 H2A histone family, member Y AD 0.008076(H2AFY) NM_017838.2 IOH4642 nucleolar protein family A, AD 0.008076member 2 (H/ACA small nucleolar RNPs) (NOLA2), transcript variant 1BC013796.1 IOH21478 adaptor-related protein complex 2, AD 0.008076 mu 1subunit (AP2M1) NM_080743.2 IOH10836 serine-arginine repressor proteinAD 0.008076 (35 kDa) (SRrp35) BC000190.1 IOH4410 zinc finger, C3HC-typecontaining AD 0.008141 1 (ZC3HC1) BC036089.1 IOH27267 myeloid/lymphoidor mixed- AD 0.008141 lineage leukemia (trithorax homolog, Drosophila);translocated to, 3 (MLLT3) NM_018215.2 IOH40888 hypothetical proteinFLJ10781 AD 0.008141 (FLJ10781), transcript variant 1 BC095401.1IOH62645 AKT-interacting protein AD 0.008141 BC006456.1 IOH5963 familywith sequence similarity Control 0.008294 21, member C (FAM21C)BC033777.2 IOH21769 amyotrophic lateral sclerosis 2 Control 0.008368(juvenile) chromosome region, candidate 8 (ALS2CR8) NM_001008572.1IOH45757 tubulin tyrosine ligase-like family, AD 0.008509 member 1(TTLL1), transcript variant 2 BC103812.1 IOH63363Alpha-ketoglutarate-dependent AD 0.008559 dioxygenase alkB homolog 3BC036365.1 IOH22309 PH domain-containing protein AD 0.008559 C10orf81NM_024718.2 IOH40918 chromosome 9 open reading frame Control 0.009125 86(C9orf86) BC013031.1 IOH13433 Pleckstrin homology-like domain Control0.009125 family B member 1 NM_022110.2 IOH10458 FK506 binding proteinlike Control 0.009125 (FKBPL) NM_016047.1 IOH11089 splicing factor 3B,14 kDa subunit AD 0.009549 (SF3B14) BC014949.1 IOH13331 DEXH(Asp-Glu-X-His) box AD 0.009549 polypeptide 58 (DHX58) BC047690.1IOH28834 Ras-related protein M-Ras AD 0.009633 NM_001894.2 IOH21160casein kinase 1, epsilon AD 0.009633 (CSNK1E), transcript variant 2NM_006482.1 Dual specificity tyrosine- AD 0.009633phosphorylation-regulated kinase 2 NM_025104.2 IOH59472 Protein DBF4homolog B AD 0.009633 BC004410.1 IOH5586 Zinc finger protein castorhomolog 1 Control 0.009819 NM_017819.1 IOH45746 RNA (guanine-9-)- AD0.009872 methyltransferase domain- containing protein 1, mitochondrialBC029382.1 IOH23139 Angiogenic factor with G patch Control 0.010166 andFHA domains 1 NM_199139.1 IOH44783 XIAP associated factor-1 (XAF1), AD0.010291 transcript variant 2 NM_003910.2 IOH23209 BUD31 homolog (S.cerevisiae) AD 0.010291 (BUD31) BC000442.1 Serine/threonine-proteinkinase 12 AD 0.010291 BC028711.2 IOH11814 cancer/testis antigen CT45-3AD 0.010291 (CT45-3) NM_018158.1 IOH38323 solute carrier family 4 (anionAD 0.010774 exchanger), member 1, adaptor protein (SLC4A1AP) BC034692.1IOH22176 anillin, actin binding protein AD 0.010774 (ANLN) NM_173605.1IOH21690 potassium channel regulator AD 0.010774 (KCNRG), transcriptvariant 1 NM_014047.1 IOH11187 chromosome 19 open reading AD 0.010774frame 53 (C19orf53) BC073791.1 IOH63073 immunoglobulin kappa constant,AD 0.010774 mRNA (cDNA clone MGC: 88809 IMAGE: 6279986), complete cdsBC014928.1 IOH10102 MYC-induced nuclear antigen AD 0.010774 BC053656.1IOH28981 EGF-like repeats and discoidin I- AD 0.010774 like domains 3(EDIL3) XM_378879.2 IOH42915 PREDICTED: Homo sapiens AD 0.010774hypothetical LOC400763 (LOC400763) NM_017817.1 IOH12515 RAB20, memberRAS oncogene AD 0.010774 family (RAB20) BC031608.1 IOH22796 RESTcorepressor 3 (RCOR3) AD 0.010774 BC047722.1 IOH26651 hypotheticalprotein MGC52110 AD 0.010774 (MGC52110) BC020726.1 IOH12969 sciellin(SCEL) AD 0.010774 NM_024039.1 IOH4379 MIS12, MIND kinetochore AD0.010774 complex component, homolog (yeast) (MIS12) BC026213.1 IOH11042F-box/WD repeat-containing AD 0.010774 protein 11 NM_002135.3 IOH10133nuclear receptor subfamily 4, AD 0.010822 group A, member 1 (NR4A1),transcript variant 1 NM_015939.2 IOH3137 tRNA methyltransferase 6 AD0.010846 homolog (S. cerevisiae) (TRMT6) NM_018039.2 IOH43857 jumonjidomain containing 2D AD 0.010846 (JMJD2D) NM_007373.2 IOH26711 soc-2suppressor of clear homolog AD 0.010846 (C. elegans) (SHOC2) BC022996.1IOH10666 SH3 domain-binding protein 2 Control 0.011036 BC067120.1IOH40451 protein tyrosine phosphatase AD 0.011036 domain containing 1,mRNA (cDNA clone MGC: 70358 IMAGE: 5539182), complete cds BC027729.1IOH14530 tetra-peptide repeat homeobox- Control 0.01201 like (TPRXL)BC054520.1 IOH28900 myocyte enhancer factor 2D Control 0.01201 (MEF2D)NM_015918.2 IOH10987 processing of precursor 5, AD 0.012016 ribonucleaseP/MRP subunit (S. cerevisiae) (POP5), transcript variant 1 NM_152677.1IOH34851 zinc finger and SCAN domain AD 0.012016 containing 4 (ZSCAN4)BC008902.2 IOH7022 GRIP and coiled-coil domain- AD 0.012016 containingprotein 1 NM_001008239.1 IOH45708 chromosome 18 open reading AD 0.012016frame 25 (C18orf25), transcript variant 2 NM_183397.1 IOH44678peroxisomal membrane protein 4, AD 0.012016 24 kDa (PXMP4), transcriptvariant 2 NM_006337.3 IOH12378 microspherule protein 1 (MCRS1), AD0.012016 transcript variant 1 NM_203305.1 IOH26383 family with sequencesimilarity Control 0.012091 102, member A (FAM102A), transcript variant2 BC034401.1 IOH22782 cDNA clone IMAGE: 5172086, AD 0.012151 partial cdsNM_006755.1 IOH2052 transaldolase 1 (TALDO1) AD 0.012151 NM_004853.1IOH9940 syntaxin 8 (STX8) AD 0.012151 BC036910.1 IOH25910 hypotheticalLOC388882 AD 0.012151 (LOC388882) BC094687.1 IOH62581 Elongation factor1-alpha 1 AD 0.012151 BC011713.2 IOH22973 tRNA methyltransferase 12Control 0.013018 homolog (S. cerevisiae) (TRMT12) NM_006263.1 IOH3647proteasome (prosome, macropain) Control 0.013018 activator subunit 1(PA28 alpha) (PSME1), transcript variant 1 NM_144608.1 IOH14178hexamthylene bis-acetamide AD 0.013303 inducible 2 (HEXIM2) NM_024038.2IOH5926 chromosome 19 open reading Control 0.013303 frame 43 (C19orf43)NM_003831.1 IOH20968 RIO kinase 3 (yeast) (RIOK3) AD 0.013332 BC020555.1IOH10305 SERPINE1 mRNA binding Control 0.013333 protein 1 (SERBP1)BC009250.1 IOH27775 guanine nucleotide binding AD 0.013333 protein-like2 (nucleolar) (GNL2) BC032598.1 IOH21976 NHL repeat containing 2 AD0.013369 (NHLRC2) NM_018697.3 IOH37734 LanC lantibiotic synthetase AD0.013369 component C-like 2 (bacterial) (LANCL2) NM_024104.1 IOH3754chromosome 19 open reading AD 0.013369 frame 42 (C19orf42) BC030665.1IOH22451 Sulfotransferase 4A1 AD 0.013369 BC004955.1 IOH5528 ATPaseinhibitory factor 1 AD 0.013369 (ATPIF1) BC009010.1 IOH3292Uncharacterized protein C6orf142 AD 0.013369 homolog BC012887.1 IOH25768Nucleolar and spindle-associated AD 0.013369 protein 1 BC015066.1IOH13784 core-binding factor, runt domain, AD 0.013369 alpha subunit 2;translocated to, 2 (CBFA2T2) BC052303.1 IOH28113 Rho GTPase activatingprotein 4 AD 0.013369 (ARHGAP4) NM_080414.1 IOH42243 vacuolar proteinsorting 16 AD 0.013369 homolog (S. cerevisiae) (VPS16), transcriptvariant 2 NM_001790.2 IOH14569 cell division cycle 25 homolog C AD0.013369 (S. pombe) (CDC25C), transcript variant 1 PHC0045 interleukin 4(IL4), transcript AD 0.013369 variant 1 NM_145041.1 IOH13199transmembrane protein 106A AD 0.013369 (TMEM106A) NM_021639.2 IOH10045GC-rich promoter binding protein AD 0.013369 1-like 1 (GPBP1L1)BC028295.1 IOH25815 peptidase D (PEPD) AD 0.013369 PV3612 aurora kinaseA (AURKA), AD 0.013369 transcript variant 2 NM_032321.1 IOH6608hypothetical protein MGC13057 AD 0.013369 (MGC13057), transcript variant4 BC010033.1 IOH27835 quinolinate AD 0.013369 phosphoribosyltransferase(nicotinate-nucleotide pyrophosphorylase (carboxylating)) (QPRT)NM_001064.1 IOH61026 Transketolase AD 0.013369 NM_017572.2 IOH53775 MAPkinase-interacting AD 0.013967 serine/threonine-protein kinase 2NM_022650.1 IOH41794 RAS p21 protein activator AD 0.013967 (GTPaseactivating protein) 1 (RASA1), transcript variant 2 NM_020781.2 IOH45442zinc finger protein 398 (ZNF398), AD 0.013967 transcript variant 2NM_182597.1 IOH44503 Coiled-coil domain-containing Control 0.014519transmembrane protein C7orf53 NM_001008211.1 IOH57143 Optineurin Control0.014972 NM_006246.2 IOH29856 protein phosphatase 2, regulatory Control0.014972 subunit B′, epsilon isoform (PPP2R5E) NM_148912.2 IOH40097abhydrolase domain containing 11 Control 0.014972 (ABHD11) BC053617.1IOH29004 B-cell CLL/lymphoma 10 Control 0.014972 (BCL10) NM_021643.1IOH21149 tribbles homolog 2 (Drosophila) Control 0.014972 (TRIB2)NM_024313.1 IOH5392 nucleolar protein 12 (NOL12) Control 0.014972NM_002735.1 IOH42254 cAMP-dependent protein kinase Control 0.014972 typeI-beta regulatory subunit NM_032929.1 IOH7540 ubiquitin specificprotease 45 Control 0.014972 (USP45) NM_024692.3 IOH42634 CAP-GLY domaincontaining Control 0.015635 linker protein family, member 4 (CLIP4)NM_002391.1 IOH13794 midkine (neurite growth- AD 0.015891 promotingfactor 2) (MDK), transcript variant 3 NM_006298.2 IOH34757 zinc fingerprotein 192 (ZNF192) AD 0.015891 BC047536.1 IOH27737 sciellin (SCEL) AD0.015891 NM_139062.1 IOH23025 casein kinase 1, delta (CSNK1D), AD0.015891 transcript variant 2 NM_005639.1 IOH29114 synaptotagmin I(SYT1) AD 0.015891 BC006811.1 IOH3174 peroxisome proliferator-activatedAD 0.015961 receptor gamma (PPARG) BC008364.1 IOH5969 heterogeneousnuclear AD 0.015961 ribonucleoprotein C (C1/C2) (HNRPC) NM_032345.1IOH6625 within bgcn homolog (Drosophila) AD 0.015961 (WIBG) BC040949.1IOH26268 myocyte enhancer factor 2D Control 0.016176 (MEF2D) NM_005522.3IOH21992 homeobox A1 (HOXA1), Control 0.016176 transcript variant 1BC016825.1 IOH14707 spire homolog 1 (Drosophila) AD 0.016623 (SPIRE1)NM_020664.3 IOH9825 2,4-dienoyl CoA reductase 2, AD 0.017399 peroxisomal(DECR2) NM_173547.2 IOH11612 tripartite motif-containing 65 Control0.017399 (TRIM65) NM_017542.3 IOH43680 pogo transposable element with AD0.017399 KRAB domain (POGK) NM_003160.1 Serine/threonine-protein kinase13 AD 0.017399 NM_032550.1 IOH10814 actin filament associated proteinControl 0.017478 1-like 2 (AFAP1L2), transcript variant 2 NM_004527.2IOH40231 mesenchyme homeobox 1 Control 0.017478 (MEOX1), transcriptvariant 1 BC031687.1 IOH21501 drebrin-like (DBNL) Control 0.017478BC026346.1 IOH10816 family with sequence similarity AD 0.017478 84,member A (FAM84A) BC041037.1 IOH28003 immunoglobulin heavy constant AD0.017478 mu (IGHM) BC028039.1 IOH11511 hypothetical protein MGC39900Control 0.01748 (MGC39900) BC033677.1 IOH40219 Uncharacterized proteinC9orf114 AD 0.017534 BC055427.1 IOH28811 TRAF2 and NCK interacting AD0.017534 kinase (TNIK) NM_016648.1 IOH41297 La ribonucleoprotein domainAD 0.017664 family, member 7 (LARP7), transcript variant 1 BC064145.1IOH40031 CDK5 regulatory subunit AD 0.017664 associated protein 1-like 1(CDKAL1) NM_138565.1 IOH6227 cortactin (CTTN), transcript AD 0.017664variant 2 NM_018441.2 IOH4050 peroxisomal trans-2-enoyl-CoA Control0.018299 reductase (PECR) NM_022823.1 IOH21980 fibronectin type IIIdomain AD 0.018299 containing 4 (FNDC4) NM_015871.2 IOH4113 zinc fingerprotein 593 (ZNF593) Control 0.01832 NM_024096.1 IOH3203XTP3-transactivated protein A Control 0.01863 (XTP3TPA) BC023546.2IOH29323 LIM and calponin homology Control 0.018757 domains 1 (LIMCH1)NM_015621.2 IOH43603 coiled-coil domain containing 69 Control 0.018757(CCDC69) BC006104.1 IOH6588 RIO kinase 1 (yeast) (RIOK1) AD 0.018757BC014975.1 IOH14285 family with sequence similarity AD 0.018844 136,member A (FAM136A) NM_138730.1 IOH9857 high mobility group nucleosomalAD 0.018844 binding domain 3 (HMGN3), transcript variant 2 BC000226.1IOH4362 ubiquitin specific peptidase 47 Control 0.019006 (USP47)NM_007242.3 IOH3925 DEAD (Asp-Glu-Ala-As) box Control 0.019006polypeptide 19B (DDX19B), transcript variant 1 NM_025004.1 IOH43200Coiled-coil domain-containing AD 0.019314 protein 15 NM_004092.2IOH54943 Enoyl-CoA hydratase, AD 0.019314 mitochondrial NM_021107.1IOH6073 mitochondrial ribosomal protein AD 0.019314 S12 (MRPS12),nuclear gene encoding mitochondrial protein, transcript variant 1NM_053049.2 IOH54667 Urocortin-3 AD 0.019314 NM_001545.1 IOH11951immature colon carcinoma AD 0.019314 transcript 1 (ICT1) NM_148571.1IOH41376 mitochondrial ribosomal protein AD 0.019314 L27 (MRPL27),nuclear gene encoding mitochondrial protein, transcript variant 2NM_001003799.1 IOH45702 TCR gamma alternate reading AD 0.019314 frameprotein (TARP), nuclear gene encoding mitochondrial protein, transcriptvariant 1 BC017227.1 IOH12094 phosducin-like (PDCL) AD 0.019314NM_172159.2 IOH25842 potassium voltage-gated channel, AD 0.019314shaker-related subfamily, beta member 1 (KCNAB1), transcript variant 3NM_000462.2 IOH38426 ubiquitin protein ligase E3A AD 0.019314 (humanpapilloma virus E6- associated protein, Angelman syndrome) (UBE3A),transcript variant 2 XM_210860.4 IOH44696 PREDICTED: Homo sapiens AD0.019314 hypothetical LOC283034 (LOC283034) BC022344.1 IOH14799twinfilin, actin-binding protein, AD 0.019314 homolog 1 (Drosophila)(TWF1) NM_005037.3 IOH39661 peroxisome proliferator-activated AD0.019314 receptor gamma (PPARG), transcript variant 4 NM_022977.1IOH42656 acyl-CoA synthetase long-chain AD 0.019314 family member 4(ACSL4), transcript variant 2 NM_006217.2 IOH11838 serpin peptidaseinhibitor, clade I AD 0.019314 (pancpin), member 2 (SERPINI2)NM_024979.2 IOH23111 Guanine nucleotide exchange AD 0.019314 factor DBSNM_016286.1 IOH4017 dicarbonyl/L-xylulose reductase AD 0.019314 (DCXR)NM_003160.1 Serine/threonine-protein kinase 13 AD 0.019314 NM_015687.2IOH38763 filamin A interacting protein 1 AD 0.019314 (FILIP1) BC005871.2IOH46098 chromosome 10 open reading AD 0.019314 frame 58 (C10orf58)NM_016216.2 IOH57112 Lariat debranching enzyme AD 0.019314 NM_017856.1IOH3877 gem (nuclear organelle) associated AD 0.019314 protein 8(GEMIN8), transcript variant 3 NM_015869.2 IOH36704 peroxisomeproliferator-activated AD 0.019314 receptor gamma (PPARG), transcriptvariant 2 NM_001003397.1 IOH58745 Tumor protein D53 AD 0.019314NM_001018061.1 IOH57329 UPF0544 protein C5orf45 AD 0.019314 [Source:UniProtKB/Swiss- Prot; Acc: Q6NTE8] NM_173060.1 IOH52621 CalpastatinControl 0.019703 BC013900.1 IOH27818 chromosome 12 open reading AD0.020182 frame 41 (C12orf41) BC022988.1 IOH22366 chromosome 6 openreading frame AD 0.020182 65 (C6orf65) NM_006299.2 IOH12838 zinc fingerprotein 193 (ZNF193) AD 0.020182 BC018847.1 IOH14862 Transaldolase AD0.020182 BC052805.1 IOH29378 erythrocyte membrane protein Control0.020182 band 4.9 (dematin) (EPB49) NM_139355.1 IOH4506megakaryocyte-associated tyrosine AD 0.0209 kinase (MATK), transcriptvariant 1 NM_207356.1 IOH40044 chromosome 1 open reading frame AD 0.0209174 (C1orf174) NM_001008737.1 IOH42047 hypothetical LOC401052 AD 0.0209(LOC401052) NM_145109.1 IOH21715 mitogen-activated protein kinase AD0.0209 kinase 3 (MAP2K3), transcript variant B BC017114.1 IOH9995oligonucleotide/oligosaccharide- AD 0.0209 binding fold containing 2A(OBFC2A) XM_086879.4 IOH43381 PREDICTED: Homo sapiens AD 0.0209hypothetical LOC150371 (LOC150371) NM_078630.1 IOH37755 male-specificlethal 3-like 1 AD 0.0209 (Drosophila) (MSL3L1), transcript variant 2NM_005197.2 IOH56874 Forkhead box protein N3 AD 0.0209 NM_004602.2IOH62672 Double-stranded RNA-binding AD 0.021101 protein Staufen homolog1 BC017504.1 IOH12256 Differentially expressed in FDCP AD 0.021101 6homolog NM_014763.2 IOH23003 mitochondrial ribosomal protein Control0.021448 L19 (MRPL19), nuclear gene encoding mitochondrial proteinNM_003590.2 IOH26262 cullin 3 (CUL3) AD 0.021703 NM_145702.1 IOH40861tigger transposable element AD 0.021703 derived 1 (TIGD1) BC001935.1IOH5068 cyclin-dependent kinase inhibitor AD 0.022172 1A (p21, Cip1)(CDKN1A) NM_031472.1 IOH5640 tRNA phosphotransferase 1 Control 0.023801(TRPT1), transcript variant 2 NM_032141.1 IOH43707 coiled-coil domaincontaining 55 Control 0.024725 (CCDC55), transcript variant 1NM_004965.3 IOH4772 high-mobility group nucleosome AD 0.024725 bindingdomain 1 (HMGN1) BC032508.1 IOH62199 PNMA-like 1, mRNA (cDNA AD 0.025032clone MGC: 45422 IMAGE: 5246377), complete cds BC013966.2 IOH12372family with sequence similarity AD 0.025523 64, member A (FAM64A)NM_020236.2 IOH13751 mitochondrial ribosomal protein AD 0.025523 L1(MRPL1), nuclear gene encoding mitochondrial protein BC043247.2 IOH28730transducin-like enhancer of split 3 AD 0.025523 (E(sp1) homolog,Drosophila) (TLE3) BC057806.1 IOH29150 insulin-like growth factorbinding AD 0.025523 protein 1 (IGFBP1) NM_006573.2 IOH12947 tumornecrosis factor (ligand) AD 0.025523 superfamily, member 13b (TNFSF13B)BC025406.1 IOH11226 phosphodiesterase 4D interacting AD 0.025523 protein(myomegalin) (PDE4DIP) BC002559.1 IOH4053 YTH domain family, member 2 AD0.025523 (YTHDF2) NM_052926.1 IOH35779 Paraneoplastic antigen-likeprotein 5 AD 0.025523 NM_006254.3 IOH26352 protein kinase C, delta(PRKCD), AD 0.025523 transcript variant 1 BC022003.1 IOH11205myotubularin related protein 9 AD 0.025523 (MTMR9) BC043348.2 IOH26348retinitis pigmentosa 2 (X-linked AD 0.025523 recessive) (RP2)NM_018010.2 IOH12676 intraflagellar transport 57 homolog AD 0.025523(Chlamydomonas) (IFT57) BC044851.1 IOH27643 vacuolar protein sorting 41AD 0.025523 homolog (S. cerevisiae) (VPS41) BC068094.1 IOH40788 SH3domain and tetratricopeptide AD 0.025523 repeats 1 (SH3TC1) NM_020961.2IOH6104 KIAA1627 protein (KIAA1627) AD 0.025523 PV3757 myosin lightchain kinase 2, AD 0.025523 skeletal muscle (MYLK2) NM_002451.3 IOH54928methylthioadenosine AD 0.025523 phosphorylase (MTAP), mRNA. NM_000281.1IOH6468 pterin-4 alpha-carbinolamine AD 0.025523dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha(TCF1) (PCBD1) NM_144982.1 IOH12275 coiled-coil domain containing 131 AD0.025523 (CCDC131) NM_017927.2 IOH43690 mitofusin 1 (MFN1), nuclear geneAD 0.025523 encoding mitochondrial protein, transcript variant 2NM_002150.1 IOH14718 4-hydroxyphenylpyruvate AD 0.025523 dioxygenaseNM_016267.1 IOH2890 vestigial like 1 (Drosophila) AD 0.025523 (VGLL1)BC067299.1 IOH40040 Mdm4, transformed 3T3 cell AD 0.025523 double minute4, p53 binding protein (mouse) (MDM4) XM_378988.2 IOH41598 PREDICTED:Homo sapiens AD 0.025523 hypothetical LOC400849 (LOC400849) NM_006466.1IOH14273 polymerase (RNA) III (DNA AD 0.025523 directed) polypeptide F,39 kDa (POLR3F) BC042608.1 IOH27462 family with sequence similarity AD0.025523 90, member A1 (FAM90A1) NM_025136.1 IOH6524 optic atrophy 3(autosomal AD 0.025523 recessive, with chorea and spastic paraplegia)(OPA3), transcript variant 2 BC012620.1 IOH12299 golgi SNAP receptorcomplex AD 0.025523 member 1 (GOSR1) NM_139244.2 IOH44877 syntaxinbinding protein 5 AD 0.025523 (tomosyn) (STXBP5) NM_015929.2 IOH7138lipoyltransferase 1 (LIPT1), AD 0.025523 transcript variant 1 PV3366v-erb-b2 erythroblastic leukemia AD 0.025523 viral oncogene homolog 2,neuro/glioblastoma derived oncogene homolog (avian) (ERBB2), transcriptvariant 2 NM_133629.1 IOH43384 RAD51-like 3 (S. cerevisiae) AD 0.025523(RAD51L3), transcript variant 4 XM_294794.1 IOH42923 PREDICTED: Homosapiens AD 0.025523 similar to putative membrane- bound dipeptidase 2(LOC339065) BC012289.1 IOH11447 KIAA0515 (KIAA0515) AD 0.025523BC029444.1 IOH23178 immunoglobulin kappa constant AD 0.025523 (IGKC)BC015109.1 IOH14036 39S ribosomal protein L1, AD 0.025523 mitochondrialNM_024578.1 IOH23128 occludin/ELL domain containing 1 AD 0.025523(OCEL1) NM_003908.1 IOH3554 eukaryotic translation initiation AD0.025523 factor 2, subunit 2 beta, 38 kDa (EIF2S2) BC001726.1 IOH4820Nucleolar protein 11 AD 0.025523 BC003666.2 IOH6106 NAD synthetase 1(NADSYN1) AD 0.025523 NM_198491.1 IOH41015 family with sequencesimilarity AD 0.025523 92, member B (FAM92B) PV3817 WEE1 homolog (S.pombe) AD 0.025523 (WEE1) BC000974.2 IOH3026 WDR45-like (WDR45L) AD0.025523 BC053675.1 IOH29030 thymopoietin (TMPO) AD 0.025523 BC033292.1IOH26782 interleukin 20 receptor beta AD 0.025523 (IL20RB) BC002509.1IOH3968 PHD finger protein 23 AD 0.025523 BC006969.1 IOH7343 dynein,cytoplasmic 2, light AD 0.025523 intermediate chain 1, mRNA (cDNA cloneMGC: 12166 IMAGE: 3828551), complete cds BC069491.1 IOH40249 Cerberus AD0.025523 NM_138559.1 IOH43559 B-cell CLL/lymphoma 11A (zinc AD 0.025523finger protein) (BCL11A), transcript variant 3 BC004376.1 IOH5584annexin A8 (ANXA8L1) AD 0.025523 NM_005620.1 IOH4079 S100 calciumbinding protein A11 AD 0.025523 (S100A11) PV3872 epidermal growth factorreceptor AD 0.025523 (erythroblastic leukemia viral (v- erb-b) oncogenehomolog, avian) (EGFR); see catalog number for detailed information onwild-type or point mutant status NM_032214.1 IOH26309 Src-like-adaptor 2(SLA2), AD 0.025523 transcript variant 1 NM_002444.1 IOH2457 moesin(MSN) AD 0.025523 NM_173796.2 IOH23049 hypothetical protein MGC24125 AD0.025523 (MGC24125) NM_002648.1 pim-1 oncogene (PIM1) AD 0.025523NM_001876.2 IOH52786 Carnitine O-palmitoyltransferase AD 0.025523 1,liver isoform BC014532.1 IOH12798 decapping enzyme, scavenger AD0.025523 (DCPS) NM_001005266.1 IOH59477 Dresden prostate carcinoma AD0.025523 protein 2 NM_007172.2 IOH40805 nucleoporin 50 kDa (NUP50), AD0.025523 transcript variant 2 NM_018326.1 IOH14251 GTPase, IMAP familymember 4 AD 0.025523 (GIMAP4) BC033881.1 IOH22099 XRCC6 binding protein1 AD 0.025523 (XRCC6BP1) NM_020168.3 IOH20961 p21(CDKN1A)-activatedkinase 6 AD 0.025523 (PAK6) NM_014790.3 IOH14698 janus kinase andmicrotubule AD 0.025562 interacting protein 2 (JAKMIP2) NM_032360.1IOH6003 acyl-Coenzyme A binding domain AD 0.025562 containing 6 (ACBD6)NM_006303.2 IOH5395 JTV1 gene (JTV1) AD 0.025562 BC017305.1 IOH12450sirtuin (silent mating type AD 0.025562 information regulation 2homolog) 7 (S. cerevisiae) (SIRT7) BC051762.1 IOH28838 Uncharacterizedprotein C20orf96 AD 0.025562 NM_145010.1 IOH10871 chromosome 10 openreading AD 0.025589 frame 63 (C10orf63) NM_206834.1 IOH40081Uncharacterized protein C6orf201 AD 0.027186 BC009350.1 IOH14087Eukaryotic translation initiation AD 0.027186 factor 2-alpha kinase 4NM_003720.1 IOH3819 Proteasome assembly chaperone 1 AD 0.027186NM_001906.1 IOH7194 chymotrypsinogen B1 (CTRB1) Control 0.027437BC037900.2 IOH27758 C-terminal binding protein 2 Control 0.027437(CTBP2) NM_138960.3 IOH59763 Homeobox protein TGIF2LX Control 0.027437BC067755.1 IOH40120 potassium channel tetramerisation AD 0.027437 domaincontaining 18 (KCTD18) BC005840.2 IOH46093 selenoprotein S (SELS) AD0.027437 BC000934.2 IOH2996 eukaryotic translation initiation AD0.027601 factor 2, subunit 2 beta, 38 kDa (EIF2S2) BC038838.1 IOH28760Proline-rich protein 16 Control 0.027601 NM_020175.1 IOH13452dihydrouridine synthase 3-like (S. cerevisiae) AD 0.027808 (DUS3L)BC002695.1 IOH5262 AP2 associated kinase 1 (AAK1) Control 0.028183NM_032472.3 IOH44558 Peptidyl-prolyl cis-trans Control 0.028183isomerase-like 3 NM_016185.1 IOH4078 hematological and neurologicalControl 0.028183 expressed 1 (HN1), transcript variant 1 BC032372.1IOH21643 Ral GEF with PH domain and Control 0.028183 SH3 binding motif 1(RALGPS1) NM_002994.2 IOH7295 chemokine (C—X—C motif) ligand 5 Control0.028183 (CXCL5) NM_176783.1 IOH40962 proteasome (prosome, macropain)Control 0.028183 activator subunit 1 (PA28 alpha) (PSME1), transcriptvariant 2 BC053872.1 IOH28961 copine V (CPNE5) Control 0.028183BC017236.1 IOH14401 Casein kinase I isoform gamma-1 Control 0.028183BC014667.1 IOH14303 immunoglobulin heavy constant AD 0.028183 gamma 1(G1m marker) (IGHG1) NM_201403.1 IOH42184 MOB1, Mps One Binder kinase AD0.028996 activator-like 2C (yeast) (MOBKL2C), transcript variant 2NM_006640.2 IOH12164 septin 9 (SEPT9) Control 0.028996 BC010537.1IOH10170 SUB1 homolog (S. cerevisiae) AD 0.029607 (SUB1) NM_170746.2IOH58679 Selenoprotein H AD 0.029607 NM_031296.1 IOH43454 RAB33B, memberRAS oncogene Control 0.030052 family (RAB33B) NM_032459.1 IOH21413embryonal Fyn-associated Control 0.030431 substrate (EFS), transcriptvariant 2 NM_003092.3 IOH21977 small nuclear ribonucleoprotein AD0.030431 polypeptide B″ (SNRPB2), transcript variant 1 NM_005105.2IOH10383 RNA binding motif protein 8A AD 0.030921 (RBM8A) BC022571.1IOH22219 prune homolog 2 (Drosophila) Control 0.031626 (PRUNE2)NM_002714.2 IOH39632 protein phosphatase 1, regulatory Control 0.031794(inhibitor) subunit 10 (PPP1R10) NM_153450.1 IOH27352 mediator complexsubunit 19 Control 0.031794 (MED19) BC104468.1 IOH63630 Outer densefiber protein 3-like Control 0.031794 protein 2 BC047411.1 IOH26516tubulin tyrosine ligase-like family, AD 0.031794 member 2 (TTLL2)NM_199188.1 IOH38224 La ribonucleoprotein domain AD 0.031794 family,member 4 (LARP4), transcript variant 2 BC003551.1 IOH4964transglutaminase 2 (C polypeptide, AD 0.032518 protein-glutamine-gamma-glutamyltransferase) (TGM2) BC020647.1 IOH12765 coiled-coil domaincontaining 59 AD 0.032518 (CCDC59) BC048301.1 IOH26612 zinc finger, CCHCdomain Control 0.032529 containing 11 (ZCCHC11) BC011781.2 IOH13131chromosome 9 open reading frame AD 0.032529 37 (C9orf37) NM_001033551.1IOH26533 TOM1-like protein 2 Control 0.032802 NM_177973.1 IOH22150sulfotransferase family, cytosolic, Control 0.032802 2B, member 1(SULT2B1), transcript variant 2 NM_006907.2 IOH59071Pyrroline-5-carboxylate reductase Control 0.032802 1, mitochondrialNM_032858.1 IOH12001 maelstrom homolog (Drosophila) AD 0.033103 (MAEL)NM_144971.1 IOH10719 hypothetical protein MGC26641 AD 0.033103(MGC26641) BC017440.1 IOH14659 trafficking protein particle AD 0.033103complex 2-like (TRAPPC2L) BC017018.1 IOH11265 DnaJ (Hsp40) homolog,subfamily AD 0.033103 C, member 12 (DNAJC12) NM_144767.3 IOH44040 Akinase (PRKA) anchor protein AD 0.033103 13 (AKAP13), transcript variant3 NM_018297.2 IOH6809 N-glycanase 1 (NGLY1) AD 0.033103 NM_031845.1IOH37776 microtubule-associated protein 2 Control 0.033103 (MAP2),transcript variant 2 NM_002307.1 IOH40009 lectin, galactoside-binding,AD 0.03362 soluble, 7 (galectin 7) (LGALS7) NM_003939.2 IOH42069beta-transducin repeat containing AD 0.03362 (BTRC), transcript variant2, mRNA. NM_013242.1 IOH5166 chromosome 16 open reading AD 0.03362 frame80 (C16orf80) NM_152285.1 IOH21698 arrestin domain containing 1 AD0.033955 (ARRDC1) NM_178425.1 IOH38634 histone deacetylase 9 (HDAC9), AD0.033955 transcript variant 5 NM_007255.1 IOH5828 xylosylprotein beta1,4- AD 0.033955 galactosyltransferase, polypeptide 7(galactosyltransferase I) (B4GALT7) NM_205833.1 IOH41224 immunoglobulinsuperfamily, AD 0.033955 member 1 (IGSF1), transcript variant 2BC040457.1 IOH26807 calcium/calmodulin-dependent AD 0.033955 proteinkinase (CaM kinase) II alpha (CAMK2A) NM_004732.1 IOH29581 potassiumvoltage-gated channel, AD 0.033955 shaker-related subfamily, beta member3 (KCNAB3) NM_004450.1 IOH14288 enhancer of rudimentary homolog AD0.033955 (Drosophila) (ERH) XM_378582.2 IOH43485 PREDICTED: Homo sapiensAD 0.033955 hypothetical LOC400523 (LOC400523) NM_001006666.1 IOH58588apolipoprotein B mRNA editing AD 0.033955 enzyme, catalyticpolypeptide-like 3F (APOBEC3F), transcript variant 2, mRNA. BC041876.1IOH27738 tau tubulin kinase 2 (TTBK2) AD 0.033955 BC036335.1 IOH25781BTB (POZ) domain containing 12 AD 0.033955 (BTBD12) BC036099.1 IOH27225aryl-hydrocarbon receptor nuclear AD 0.033955 translocator 2 (ARNT2)NM_054012.1 IOH14007 argininosuccinate synthetase 1 AD 0.033955 (ASS1),transcript variant 2 NM_057749.1 IOH43526 cyclin E2 (CCNE2) AD 0.033955PV3839 CDC-like kinase 4 (CLK4) AD 0.033955 BC005026.1 IOH6532 sirtuin(silent mating type AD 0.033955 information regulation 2 homolog) 6 (S.cerevisiae) (SIRT6) NM_013975.1 IOH40893 ligase III, DNA, ATP-dependentAD 0.033955 (LIG3), nuclear gene encoding mitochondrial protein,transcript variant alpha NM_181509.1 IOH42908 microtubule-associatedprotein 1 AD 0.033955 light chain 3 alpha (MAP1LC3A), transcript variant2 BC001709.1 IOH4911 NAD kinase (NADK) AD 0.033955 NM_002638.1 IOH13658peptidase inhibitor 3, skin-derived AD 0.033955 (SKALP) (PI3)NM_005901.2 IOH22138 SMAD family member 2 AD 0.033955 (SMAD2),transcript variant 1 BC046199.1 IOH26969 family with sequence similarityAD 0.033955 72, member B (FAM72B) NM_015417.2 IOH11253 sperm flagellar 1(SPEF1) AD 0.033955 NM_018328.1 IOH12893 methyl-CpG binding domain AD0.033955 protein 5 (MBD5) BC017328.2 IOH14721 angiotensin IIreceptor-associated AD 0.033955 protein (AGTRAP) NM_182739.1 IOH44393NADH dehydrogenase AD 0.033955 (ubiquinone) 1 beta subcomplex, 6, 17 kDa(NDUFB6), nuclear gene encoding mitochondrial protein, transcriptvariant 2 NM_001032293.1 IOH3584 zinc finger protein 207 (ZNF207), AD0.033955 transcript variant 2 NM_012227.1 IOH57121 Putative GTP-bindingprotein 6 AD 0.033955 BC026039.1 IOH40656 mitochondrial GTPase 1 homologAD 0.033955 (S. cerevisiae) (MTG1) BC072409.1 IOH62546Serine/threonine-protein AD 0.033955 phosphatase 4 regulatory subunit 3ABC066938.1 IOH40083 DEAD (Asp-Glu-Ala-Asp) box AD 0.034253 polypeptide43 (DDX43) BC000712.1 IOH4703 kinesin family member C1 AD 0.034253(KIFC1) BC000052.1 IOH4650 peroxisome proliferator-activated AD 0.035152receptor alpha (PPARA) NM_199124.1 IOH43439 chromosome 11 open readingControl 0.035152 frame 63 (C11orf63), transcript variant 2 NM_004117.2IOH27424 FK506 binding protein 5 (FKBP5) AD 0.035152 NM_002629.2IOH13682 phosphoglycerate mutase 1 (brain) AD 0.035152 (PGAM1)NM_015122.1 IOH26137 FCH domain only 1 (FCHO1) AD 0.035152 NM_001021.2IOH27847 ribosomal protein S17 (RPS17) AD 0.035152 NM_013323.1 IOH3822sorting nexin 11 (SNX11), AD 0.035152 transcript variant 2 BC002950.1IOH46164 chromosome 18 open reading AD 0.035152 frame 8 (C18orf8)NM_017612.1 IOH11180 Zinc finger CCHC domain- AD 0.035152 containingprotein 8 BC035048.2 IOH27687 neurogenic differentiation 6 AD 0.035152(NEUROD6) BC046117.1 IOH26985 dynein, axonemal, light AD 0.035152intermediate chain 1 (DNALI1) NM_005335.3 IOH57089 Hematopoietic lineagecell- AD 0.035152 specific protein NM_144679.1 IOH40679 chromosome 17open reading AD 0.035152 frame 56 (C17orf56) NM_004881.1 IOH3658 tumorprotein p53 inducible AD 0.035152 protein 3 (TP53I3), transcript variant1 NM_006442.2 IOH14520 DR1-associated protein 1 Control 0.035766(negative cofactor 2 alpha) (DRAP1) BC047733.1 IOH26736 tRNA asparticacid Control 0.035766 methyltransferase 1 (TRDMT1) NM_033122.1 IOH26918chromosome 4 open reading frame Control 0.035766 35 (C4orf35)NM_080423.1 IOH23012 protein tyrosine phosphatase, non- Control 0.035766receptor type 2 (PTPN2), transcript variant 3 BC015665.2 IOH40642 LATS,large tumor suppressor, Control 0.035766 homolog 1 (Drosophila) (LATS1)BC001716.1 IOH4447 poly(A) binding protein Control 0.035766 interactingprotein 2 (PAIP2) NM_138316.2 IOH59336 Pantothenate kinase 1 Control0.035766 NM_005900.1 IOH4970 SMAD family member 1 Control 0.035766(SMAD1), transcript variant 1 BC039337.1 IOH62273 Polyadenylate-bindingprotein- Control 0.035766 interacting protein 2 NM_001950.3 IOH23241 E2Ftranscription factor 4, Control 0.035766 p107/p130-binding (E2F4)BC008819.1 IOH6323 nuclear receptor subfamily 1, Control 0.035766 groupH, member 3 (NR1H3) NM_024818.1 IOH9860 ubiquitin-activating enzyme E1-Control 0.035766 domain containing 1 (UBE1DC1), transcript variant 1NM_004838.2 IOH12410 homer homolog 3 (Drosophila) Control 0.035766(HOMER3) NM_012419.3 IOH11052 regulator of G-protein signaling 17Control 0.035766 (RGS17) BC042999.2 IOH25869 Putative Polycomb groupprotein Control 0.035766 ASXL2 NM_005441.2 IOH13577 chromatin assemblyfactor 1, Control 0.035766 subunit B (p60) (CHAF1B) BC009055.1 IOH3376Protein FAM184A Control 0.035766 BC006818.1 IOH31861-acylglycerol-3-phosphate O- Control 0.035766 acyltransferase 1(lysophosphatidic acid acyltransferase, alpha), mRNA (cDNA clone IMAGE:3448169), complete cds. BC053509.1 IOH293945,10-methylenetetrahydrofolate Control 0.035766 reductase (NADPH)(MTHFR) BC051888.1 IOH27068 tRNA-yW synthesizing protein 1 Control0.035766 homolog (S. cerevisiae) (TYW1) NM_001952.2 IOH6989 E2Ftranscription factor 6 (E2F6) Control 0.035766 PV3871 dual-specificitytyrosine-(Y)- Control 0.035766 phosphorylation regulated kinase 4(DYRK4) BC012746.1 IOH14565 mesoderm development candidate Control0.035766 2 (MESDC2) NM_003341.3 IOH43236 Ubiquitin-conjugating enzyme E2Control 0.035766 E1 NM_138499.2 IOH40143 PWWP domain-containing proteinControl 0.035766 2B NM_032051.1 IOH13231 POZ (BTB) and AT hook Control0.035766 containing zinc finger 1 (PATZ1), transcript variant 4BC007565.1 IOH6820 phospholipase C, gamma 2 Control 0.035766(phosphatidylinositol-specific) (PLCG2) NM_022083.1 IOH45531 ProteinNiban Control 0.035766 NM_052940.3 IOH10671 leucine rich repeatcontaining 42 Control 0.035766 (LRRC42) BC044884.1 IOH26494 KIAA0265protein (KIAA0265) Control 0.035766 BC000452.1 IOH3518 peroxiredoxin 2(PRDX2) Control 0.035766 NM_018246.1 IOH40864 coiled-coil domaincontaining 25 Control 0.035766 (CCDC25) BC005033.1 IOH6631 actinin,alpha 4 (ACTN4) Control 0.035766 BC000583.1 IOH22887 Thimetoligopeptidase Control 0.035766 NM_006406.1 IOH7551 peroxiredoxin 4(PRDX4) Control 0.035766 BC034488.2 IOH22312 ATP-binding cassette,sub-family Control 0.035766 F (GCN20), member 1 (ABCF1) BC020942.1IOH11137 transmembrane protein 140 Control 0.035766 (TMEM140)NM_003223.1 IOH9646 transcription factor AP-4 Control 0.035766(activating enhancer binding protein 4) (TFAP4) BC011863.2 IOH14833 DNAhelicase HEL308 (HEL308) Control 0.035766 NM_025057.1 IOH35314chromosome 14 open reading Control 0.035766 frame 45 (C14orf45)NM_031361.1 IOH4674 collagen, type IV, alpha 3 Control 0.035766(Goodpasture antigen) binding protein (COL4A3BP), transcript variant 2NM_052965.1 IOH56031 tRNA-splicing endonuclease Control 0.035766 subunitSen15 NM_199334.2 IOH6734 thyroid hormone receptor, alpha AD 0.037822(erythroblastic leukemia viral (v- erb-a) oncogene homolog, avian)(THRA), transcript variant 1 NM_201567.1 IOH37812 cell division cycle 25homolog A AD 0.037822 (S. pombe) (CDC25A), transcript variant 2BC012945.1 IOH25802 Uncharacterized protein C19orf57 AD 0.038115NM_005663.2 IOH46152 Wolf-Hirschhorn syndrome Control 0.038115 candidate2 (WHSC2) BC025266.1 IOH23199 taspase, threonine aspartase, 1 Control0.038169 (TASP1) NM_014487.2 IOH4416 zinc finger protein 330 (ZNF330)Control 0.038169 NM_197957.2 IOH41003 MYC associated factor X (MAX),Control 0.038169 transcript variant 6 NM_006695.2 IOH5798 RUN domaincontaining 3A Control 0.038169 (RUNDC3A) NM_144594.1 IOH10942 familywith sequence similarity Control 0.038169 112, member B (FAM112B)NM_032146.2 IOH10608 ADP-ribosylation factor-like 6 Control 0.038169(ARL6), transcript variant 1 BC014218.2 IOH12802 THAP domain-containingprotein 3 Control 0.038169 BC037845.1 IOH62213 Multiple coagulationfactor Control 0.038169 deficiency protein 2 BC043394.1 IOH26350 ankyrinrepeat domain 17 AD 0.040087 (ANKRD17) NM_053005.2 IOH40119 HCCA2protein (HCCA2) AD 0.040087 NM_175065.2 IOH35055 histone cluster 2, H2abAD 0.040087 (HIST2H2AB) NM_004706.3 IOH45526 Rho guanine nucleotideexchange AD 0.040087 factor (GEF) 1 (ARHGEF1), transcript variant 2NM_014346.1 IOH22792 TBC1 domain family, member AD 0.040087 22A(TBC1D22A) NM_133480.1 IOH13139 transcriptional adaptor 3 (NGG1 AD0.040118 homolog, yeast)-like (TADA3L), transcript variant 2 BC002448.2IOH4300 actin binding LIM protein 1 Control 0.041317 (ABLIM1) BC048969.1IOH26897 TSPY-like 1 (TSPYL1) AD 0.041317 NM_020319.1 IOH27320 ankyrinrepeat and MYND domain AD 0.041317 containing 2 (ANKMY2) NM_016046.2IOH11580 exosome component 1 (EXOSC1) AD 0.042299 NM_001003396.1 IOH3597tumor protein D52-like 1 AD 0.042315 (TPD52L1), transcript variant 3NM_005870.3 IOH53845 Histone deacetylase complex AD 0.042315 subunitSAP18 NM_003403.3 IOH27684 YY1 transcription factor (YY1) AD 0.042315BC036096.2 IOH27280 zinc finger protein 18 (ZNF18) AD 0.042315NM_001010844.1 IOH43230 Interleukin-1 receptor-associated AD 0.043024kinase 1-binding protein 1 BC029524.1 IOH22562 Coiled-coildomain-containing AD 0.04393 protein 46 NM_005884.2 IOH2475p21(CDKN1A)-activated kinase 4 Control 0.04393 (PAK4), transcriptvariant 1 NM_033642.1 IOH36760 fibroblast growth factor 13 Control0.045355 (FGF13), transcript variant 1B BC058900.1 IOH29076 rabaptin,RAB GTPase binding Control 0.045355 effector protein 2 (RABEP2)BC015239.1 IOH10789 zinc finger and BTB domain Control 0.045355containing 8 (ZBTB8) NM_001005339.1 IOH13018 regulator of G-proteinsignaling 10 Control 0.045355 (RGS10), transcript variant 1 NM_006819.1IOH5061 stress-induced-phosphoprotein 1 Control 0.045355(Hsp70/Hsp90-organizing protein) (STIP1) NM_152387.2 IOH53987 BTB/POZdomain-containing AD 0.045355 protein KCTD18 BC002369.1Serine/threonine-protein kinase AD 0.045355 PLK1 BC092404.1 IOH62574 Rapguanine nucleotide exchange AD 0.045786 factor 3 NM_004922.2 IOH38664SEC24 related gene family, AD 0.046722 member C (S. cerevisiae)(SEC24C), transcript variant 1 NM_198217.1 IOH59743 Inhibitor of growthprotein 1 AD 0.046722 BC051911.1 IOH27047 chromosome 13 open reading AD0.046722 frame 24 (C13orf24) NM_006205.1 IOH40356 phosphodiesterase 6H,cGMP- AD 0.046722 specific, cone, gamma (PDE6H) NM_024790.2 IOH13277centrosome and spindle pole Control 0.046828 associated protein 1(CSPP1), transcript variant 2 NM_006439.3 IOH12221 Protein mab-21-like 2AD 0.046828 NM_173456.1 IOH45493 phosphodiesterase 8A (PDE8A), AD0.048209 transcript variant 4 BC019268.1 IOH13177 Protein arginine N- AD0.048209 methyltransferase 1 NM_173642.1 IOH26158 family with sequencesimilarity AD 0.048209 80, member A (FAM80A) NM_194299.1 IOH35431Synaptonemal complex protein 2- AD 0.048209 like BC062323.1 IOH40678chromosome 21 open reading AD 0.048209 frame 25 (C21orf25) NM_021709.1IOH21450 Apoptosis regulatory protein Siva AD 0.048209 BC100813.1IOH63506 Putative T-complex protein 1 AD 0.048209 subunit theta-like 2BC026317.1 IOH11060 solute carrier family 16, member 1 AD 0.048209(monocarboxylic acid transporter 1) (SLC16A1) BC010956.1 IOH13684Keratinocyte growth factor AD 0.048209 NM_005034.2 IOH10479 polymerase(RNA) II (DNA AD 0.048209 directed) polypeptide K, 7.0 kDa (POLR2K)BC024291.1 IOH14775 BR serine/threonine kinase 2 AD 0.048209 (BRSK2)NM_001001568.1 IOH53504 phosphodiesterase 9A (PDE9A), AD 0.048209transcript variant 3, mRNA. NM_014314.3 IOH52971 Probable ATP-dependentRNA AD 0.048209 helicase DDX58 BC047420.1 IOH26512 UBX domain-containingprotein 7 AD 0.048209 NM_000430.2 IOH39940 platelet-activating factor AD0.048209 acetylhydrolase, isoform Ib, alpha subunit 45 kDa (PAFAH1B1)PV3873 epidermal growth factor receptor AD 0.048209 (erythroblasticleukemia viral (v- erb-b) oncogene homolog, avian) (EGFR); see catalognumber for detailed information on wild-type or point mutant statusNM_001328.1 IOH12818 C-terminal binding protein 1 AD 0.048209 (CTBP1),transcript variant 1 NM_001009959.1 IOH43447 Ermin AD 0.048209BC050387.1 IOH26653 ankyrin repeat and sterile alpha AD 0.048209 motifdomain containing 3 (ANKS3) NM_007194.1 Serine/threonine-protein kinaseAD 0.048209 Chk2 NM_018492.2 IOH12390 PDZ binding kinase (PBK) AD0.048209 NM_182801.1 IOH23237 EGF-like, fibronectin type III and AD0.048209 laminin G domains (EGFLAM), transcript variant 4 BC016615.1IOH10688 RAB37, member RAS oncogene AD 0.048209 family (RAB37)BC008950.2 IOH56909 Prenylated Rab acceptor protein 1 AD 0.048209BC041831.1 IOH27713 transducin-like enhancer of split 3 AD 0.048209(E(sp1) homolog, Drosophila) (TLE3) NM_003104.2 IOH14671 sorbitoldehydrogenase (SORD) AD 0.048209 BC003555.1 IOH4980 nucleolar complexassociated 2 AD 0.048209 homolog (S. cerevisiae) (NOC2L) NM_001274.2CHK1 checkpoint homolog (S. pombe) AD 0.048209 (CHEK1) NM_153645.1IOH11663 nucleoporin 50 kDa (NUP50), AD 0.048209 transcript variant 3BC017423.1 IOH12806 mesoderm induction early AD 0.048209 response 1homolog (Xenopus laevis) (MIER1) BC007424.2 IOH6160 PRP4 pre-mRNAprocessing AD 0.048209 factor 4 homolog (yeast) (PRPF4) NM_007107.2IOH13133 signal sequence receptor, gamma AD 0.048209(translocon-associated protein gamma) (SSR3) XM_096472.2 IOH42996hypothetical LOC143678 AD 0.048209 (LOC143678) NM_015698.2 IOH3563 Gpatch domain and KOW motifs AD 0.048209 (GPKOW) NM_018111.1 IOH57283Putative uncharacterized protein AD 0.048209 FLJ10490 NM_006694.1IOH2941 jumping translocation breakpoint AD 0.048209 (JTB) NM_000045.2IOH14233 arginase, liver (ARG1) AD 0.048209 BC074765.2 IOH59064 POUdomain, class 6, transcription AD 0.048209 factor 1 NM_172028.1 IOH42497ankyrin repeat and BTB (POZ) AD 0.048209 domain containing 1 (ABTB1),transcript variant 3 BC026345.1 IOH10790 Ermin AD 0.048209 NM_201262.1IOH41260 DnaJ (Hsp40) homolog, subfamily AD 0.048209 C, member 12(DNAJC12), transcript variant 2 NM_002966.1 IOH14651 S100 calciumbinding protein A10 AD 0.048209 (S100A10) BC013352.1 IOH14736 HpaII tinyfragments locus 9c AD 0.048209 protein NM_004873.1 IOH26366BCL2-associated athanogene 5 AD 0.048209 (BAG5), transcript variant 2BC009415.1 IOH14115 kinesin family member 26A AD 0.048209 (KIF26A)BC012539.1 IOH12758 mediator complex subunit 31 AD 0.048209 (MED31)BC021247.1 IOH22996 Phosphatase and actin regulator 4 AD 0.048209NM_004414.3 IOH5722 regulator of calcineurin 1 AD 0.048209 (RCAN1),transcript variant 1 BC028840.1 IOH13887 ankyrin repeat domain 13C AD0.048209 (ANKRD13C) BC025787.1 IOH12000 alkB, alkylation repair homolog1 AD 0.048209 (E. coli) (ALKBH1) NM_000459.1 Angiopoietin-1 receptor AD0.048209 NM_000788.1 IOH42066 Deoxycytidine kinase AD 0.048209NM_173859.1 IOH35196 breast cancer and salivary gland AD 0.048209expression gene (RP11-49G10.8) NM_152382.1 IOH39899 JmjCdomain-containing protein AD 0.048209 C2orf60 NM_002038.2 IOH14517interferon, alpha-inducible protein AD 0.048209 6 (IFI6), transcriptvariant 1 BC034984.1 IOH26875 Kinesin-like protein KIF16B AD 0.048209NM_014582.1 IOH40248 odorant binding protein 2A AD 0.048209 (OBP2A)BC057760.1 IOH29220 MORN repeat-containing protein 3 AD 0.048209NM_005595.1 IOH12791 nuclear factor I/A (NFIA) AD 0.048209 NM_032726.1IOH21106 phospholipase C, delta 4 (PLCD4) AD 0.048209 NM_153276.1IOH21851 solute carrier family 22 (organic AD 0.048209 aniontransporter), member 6 (SLC22A6), transcript variant 2 NM_001011538.1IOH39826 similar to 60S ribosomal protein AD 0.048209 L21 (LOC402176)NM_006433.2 IOH27865 granulysin (GNLY), transcript AD 0.048209 variantNKG5 NM_024800.1 Serine/threonine-protein kinase AD 0.048209 Nek11NM_015850.2 Basic fibroblast growth factor AD 0.048209 receptor 1NM_006590.2 IOH45672 ubiquitin specific peptidase 39 AD 0.048209 (USP39)NM_199054.1 IOH37765 MAP kinase interacting AD 0.048209 serine/threoninekinase 2 (MKNK2), transcript variant 2 BC050696.1 IOH27004 chromosome 12open reading AD 0.048209 frame 48 (C12orf48) NM_024563.1 IOH23059chromosome 5 open reading frame AD 0.048209 23 (C5orf23) NM_004832.1IOH4381 glutathione S-transferase omega 1 AD 0.048209 (GSTO1)NM_003242.2 transforming growth factor, beta AD 0.048209 receptor II(70/80 kDa) (TGFBR2), transcript variant 2 BC050444.1 IOH26738 golgiautoantigen, golgin AD 0.048209 subfamily a, 4 (GOLGA4) NM_201259.1IOH45586 Mitochondrial import inner AD 0.048209 membrane translocasesubunit TIM14 NM_032124.3 IOH27146 haloacid dehalogenase-like AD0.048209 hydrolase domain containing 2 (HDHD2) NM_002870.1 IOH3059RAB13, member RAS oncogene AD 0.048209 family (RAB13) BC000337.2 IOH3577glucose-6-phosphate AD 0.048209 dehydrogenase (G6PD) BC060785.1 IOH29158tripartite motif-containing 40 AD 0.048209 (TRIM40) BC030597.1 IOH22318ATR interacting protein (TREX1) AD 0.048209 BC050551.1 IOH26948BCL2-associated athanogene 5 AD 0.048209 (BAG5) NM_004697.3 IOH12861PRP4 pre-mRNA processing AD 0.048209 factor 4 homolog (yeast) (PRPF4)NM_020990.2 IOH5022 creatine kinase, mitochondrial 1B AD 0.048209(CKMT1B), nuclear gene encoding mitochondrial protein BC039742.1IOH26173 poly(rC) binding protein 1 AD 0.048209 (PCBP1) BC021573.1IOH14848 GTP-binding protein 10 AD 0.048209 NM_015068.1 IOH27074paternally expressed 10 (PEG10), AD 0.048209 transcript variant 1NM_001827.1 IOH5978 CDC28 protein kinase regulatory AD 0.048209 subunit2 (CKS2) NM_152876.1 IOH50154 Tumor necrosis factor receptor AD 0.048209superfamily member 6 BC015548.1 IOH10351 RAB3A interacting protein AD0.048209 (rabin3) (RAB3IP) BC062359.1 IOH40676 chromosome 8 open readingframe AD 0.048209 47 (C8orf47) BC029424.1 IOH23140 Probable glutathioneperoxidase 8 AD 0.048209 NM_001786.2 IOH14583 cell division cycle 2, G1to S and AD 0.048209 G2 to M (CDC2), transcript variant 1 BC000870.1IOH3246 TIMELESS interacting protein AD 0.048209 (TIPIN) NM_004103.2Protein tyrosine kinase 2 beta AD 0.048209 BC022454.2 IOH10977 Transientreceptor potential cation AD 0.048209 channel subfamily M member 3NM_024046.1 IOH21132 CaM kinase-like vesicle- AD 0.048209 associated(CAMKV) BC040521.1 IOH27477 testis expressed 2 (TEX2) AD 0.048209BC003164.1 IOH46140 leukocyte receptor cluster (LRC) AD 0.048209 member4 (LENG4) NM_000402.2 IOH2390 Glucose-6-phosphate 1- AD 0.048209dehydrogenase BC069328.1 IOH40255 Bcl2 modifying factor (BMF) AD0.048209 BC063463.1 IOH39865 coenzyme Q3 homolog, AD 0.048209methyltransferase (S. cerevisiae) (COQ3) NM_000572.2 IOH29878Interleukin-10 AD 0.048209 NM_006374.2 serine/threonine kinase 25 (STE20AD 0.048209 homolog, yeast) (STK25) NM_017966.1 IOH5829 vacuolar proteinsorting 37 AD 0.048209 homolog C (S. cerevisiae) (VPS37C) BC052602.1IOH29373 carbonic anhydrase XIII (CA13) AD 0.048209 BC018063.1 IOH10722potassium channel tetramerisation AD 0.048209 domain containing 4(KCTD4) NM_031305.1 IOH38124 Rho GTPase activating protein 24 AD0.048209 (ARHGAP24), transcript variant 2 BC056401.1 IOH28794 centaurin,delta 2 (CENTD2) AD 0.048209 BC022459.1 IOH11064 sulfotransferase family4A, AD 0.048209 member 1 (SULT4A1) XM_373630.2 IOH41531 PREDICTED: Homosapiens AD 0.048209 hypothetical protein LOC145842 (LOC145842) P3049v-abl Abelson murine leukemia AD 0.048209 viral oncogene homolog 1(ABL1), transcript variant a; see catalog number for detailedinformation on wild-type or point mutant status NM_153012.1 IOH12147Tumor necrosis factor ligand AD 0.048209 superfamily member 12NM_018270.3 IOH14702 MRG-binding protein AD 0.048209 BC010739.1 IOH9887COP9 signalosome complex AD 0.048209 subunit 7b NM_015002.2 IOH42260F-box protein 21 (FBXO21), AD 0.048209 transcript variant 2 BC000497.1CaM kinase-like vesicle- AD 0.048209 associated protein NM_001449.2IOH13860 four and a half LIM domains 1 AD 0.048209 (FHL1) BC065912.1IOH40442 Tyrosine-protein kinase ABL2 AD 0.048209 NM_153356.1 IOH27369TBC1 domain family, member 21 AD 0.048209 (TBC1D21) BC032382.1 IOH21661similar to pleckstrin homology AD 0.048209 domain containing, family M(with RUN domain) member 1; adapter protein 162, mRNA, complete cds.BC094800.1 IOH62619 Jouberin AD 0.048362 NM_207035.1 IOH41684 UPF0471protein C1orf63 Control 0.048362 homolog NM_003897.2 IOH6603 immediateearly response 3 (IER3) AD 0.048717 NM_178821.1 IOH22298 WD repeatdomain 69 (WDR69) AD 0.048717 NM_198219.1 IOH59467 Inhibitor of growthprotein 1 AD 0.048717 NM_024805.1 IOH13501 chromosome 18 open reading AD0.048717 frame 22 (C18orf22) NM_001040633.1 IOH61663 protein kinase,AMP-activated, AD 0.048717 gamma 2 non-catalytic subunit (PRKAG2),transcript variant c, mRNA. NM_130807.1 IOH10112 MOB1, Mps One Binderkinase AD 0.049919 activator-like 2A (yeast) (MOBKL2A) BC008623.1IOH3309 roundabout, axon guidance AD 0.049919 receptor, homolog 3(Drosophila) (ROBO3) NM_001004285.1 IOH45460 DNA fragmentation factor,40 kDa, AD 0.049919 beta polypeptide (caspase- activated DNase) (DFFB),transcript variant 3 BC011885.1 IOH14206 eukaryotic translationinitiation AD 0.049919 factor 2A, 65 kDa (EIF2A)

Using a small subset of the identified indicators, it was possible todiagnose AD with great efficiency. The twenty protein microarrayfluorescence values depicted in Table 4 were used to classify blindedsamples as either Alzheimer's or control. A threshold value wascalculated for each diagnostic indicator using the following equation:Diagnostic Threshold=[(Mean AD Fluorescence Value)−(Mean ControlFluorescence Value)/2]+(Mean Control Fluorescence Value)

A fluorescence value for any given diagnostic indicator over thethreshold value for that indicator is scored as a positive result. Usingthe antigens from Table 4, greater than or equal to four positiveresults out of the possible twenty diagnostic indicators predicts withhigh accuracy that the sample is from an Alzheimer's Disease patient.Less than four positive results out of the possible twenty diagnosticindicators on Table 4 predicts with high accuracy that the sample isfrom a healthy Control. (See FIG. 1.) Initial results with thisdiagnostic logic were as follows:

Alzheimer's Disease (AD) vs. All Controls

(Using twenty biomarkers from Table 4)

(See FIG. 1)

N=90 (50 AD, 40 Control)

Overall Error Rate: 4.44%

Predicted/True AD Control AD 50 4 Control 0 36 Error Rate 0.000 0.010

Example 9 Diagnosis of Alzheimer's Disease

Twenty antibodies and their respective antigens were selected that wererated as highly significant by multiple statistical analysis programs(Prospector, PAM, Random Forest) and performed well in a singleplatform. The antibodies are listed in Table 8.

TABLE 8 Diagnostic Autoantibodies in Alzheimer's Disease MW Database ID#: Name: (kDa): Indication: Reactivity: BC051695.1 FRMD8 51.2Alzheimer's ↑ AD, ↓CON NM_015833.1 ADARB1 80.8 Alzheimer's ↑ AD, ↓CONNM_002305.2 LGALS1 14.7 Alzheimer's ↑ AD, ↓CON NM_001641.2 APEX1 35.6Alzheimer's ↑ AD, ↓CON NM_024316.1 LENG1 30.5 Control ↓ AD, ↑CONNM_014280.1 DnaJ 29.8 Alzheimer's ↑ AD, ↓CON homolog subfamily C member8 PHC1244 CCL19 11.0 Alzheimer's ↑ AD, ↓CON BC064984.1 ASXL1 9.5Alzheimer's ↑ AD, ↓CON NM_021104.1 RPL41 3.4 Alzheimer's ↑ AD, ↓CONBC004236.2 UBE2S 23.9 Alzheimer's ↑ AD, ↓CON NM_012387.1 PADI4 74.1Alzheimer's ↑ AD, ↓CON NM_003384.1 VRK1 45.5 Alzheimer's ↑ AD, ↓CONNM_004113.3 FGF12 27.4 Alzheimer's ↑ AD, ↓CON BC021174.1 Small 12.4Alzheimer's ↑ AD, ↓CON EDRK-rich factor 1 NM_001001794.1 FAM116B 66.5Alzheimer's ↑ AD, ↓CON NM_032377.2 ELOF1 9.5 Alzheimer's ↑ AD, ↓CONNM_024754.2 PTCD2 43.9 Alzheimer's ↑ AD, ↓CON NM_000984.2 RPL23A 17.7Alzheimer's ↑ AD, ↓CON NM_139016.2 C20orf198 Alzheimer's ↑ AD, ↓CONNM_024668.1 ANKHD1 269.5 Alzheimer's ↑ AD, ↓CON

With these twenty biomarkers (listed in Table 4 and Table 8) and thesimple diagnostic logic explained above, it was possible todifferentiate Alzheimer's Disease serum samples from Control serumsamples with over 95% efficiency.

It is also possible to accurately diagnose using only the fourbiomarkers from Table 3. Diagnostic efficiency for these diagnosticindicators was assessed for AD, low Mini-Mental Status Examination(MMSE) AD and high-MMSE AD. The results are shown below.

Alzheimer's Disease (AD) vs. All Controls

Random Forest:

N=90 (50 AD, 40 Control)

Overall Error Rate: 7.78%

Predicted/True AD Control AD 48 5 Control 2 35 Error Rate 0.040 0.125Predictive Analysis of Microarrays (PAM):N=90 (50 AD, 40 Con)Overall Error Rate: 7.8%

Predicted/True AD Control AD 50    7    Control 0    33    Error Rate0.000 0.175Low-MMSE AD vs. All Controls

(Low-MMSE AD samples have MMSE<15)

Random Forest:

N=55 (15 Low-MMSE AD, 40 Control)

Overall Error Rate: 7.26%

Predicted/True AD Control AD 13    2    Control 2    38    Error Rate0.133 0.050Predictive Analysis of Microarrays (PAM):N=30 (15 Low-MMSE AD, 15 Control)Overall Error Rate: 9.9%

Predicted/True AD Control AD 13    1    Control 2    14    Error Rate0.133 0.067High-MMSE AD vs. All Controls

(High-MMSE AD samples have MMSE≧15)

Random Forest:

N=75 (35 High-MMSE AD, 40 Control)

Overall Error Rate: 10.67%

Predicted/True AD Control AD 32    5    Control 3    35    Error Rate0.086 0.125Predictive Analysis of Microarrays (PAM):N=70 (35 High-MMSE AD, 35 Control)Overall Error Rate: 12.8%

Predicted/True AD Control AD 28    2    Control 7    33    Error Rate0.200 0.057

Using a combination of the biomarkers listed in Tables 3 and 5 (totalingnine diagnostic indicators), the efficiency of distinction between ADand Parkinson's Disease was also assessed. The results are shown below.

Alzheimer's Disease (AD) vs. Parkinson's Disease (PK)

Random Forest:

N=79 (29 AD, 29 PK)

Overall Error Rate: 12.07%

Predicted/True AD PK AD 25    3    PK 4    26    Error Rate 0.138 0.103Predictive Analysis of Microarrays (PAM):N=58 (29 AD, 29 PK)Overall Error Rate: 12.0%

Predicted/True AD PK AD 24    2    PK 5    27    Error Rate 0.172 0.069

It was determined that it was possible to differentiate AD and controlwith over 95% accuracy using the twenty antigens from Table 4 and over90% accuracy using the four antigens on Table 3, however, the use ofonly these four indicators did not allow accurate differentiation ofAlzheimer's Disease from other neurodegenerative diseases likeParkinson's Disease. Accurate differentiation requires the inclusion ofantigens from Table 5. In practice, however, this distinction is oftenunnecessary, since patients presenting with suspected Alzheimer'sdisease come with memory and cognitive deficits, whereas patients withearly Parkinson's most often show tremors with no complaints ofcognitive and/or memory deficits.

All references cited herein are incorporated by reference herein intheir entireties.

The invention claimed is:
 1. A method for detecting neurodegenerativedisease diagnostic autoantibodies in a subject in need thereofcomprising: (a) obtaining an immunoglobulin-containing biological samplefrom the subject, and (b) performing an assay on said biological sampleto determine the presence of autoantibodies in the biological sample,wherein said assay comprises the steps of: (i) forming immunocomplexesbetween autoantibodies targeting at least two autoantigens selected fromthe group consisting of centaurin, alpha 2 (CENTA 2), jumonji domaincontaining 2D (JMJD2D); pentatricopeptide repeat domain 2 (PTCD2);lectin, galactoside-binding, soluble, 1 (galectin 1)(LGALS1); andregulating synaptic membrane exocytosis 4 (RIMS4); and (ii) detectingthe presence of said immunocomplexes.
 2. The method of claim 1, whereinsaid subject is a human.
 3. The method of claim 1, wherein saidbiological sample is selected from the group consisting of whole blood,serum, cerebrospinal fluid, saliva, and sputum.
 4. The method of claim 1wherein the autoantigens are attached to a substrate and are in the formof an array.
 5. The method of claim 4 wherein the array is a microarray.6. The method of claim 5, wherein said microarray contains up to 882autoantigens.
 7. The method of claim 5, wherein said microarray furthercontains an additional autoantigen selected from the group consisting ofpentatricopeptide repeat domain 2 (PTCD2); FERM domain containing 8(FRMD8); chromosome 9 open reading frame 9 (C9orf9); lectin,galactoside-binding, soluble, 1 (galectin 1) (LGALS1);proopiomelanocortin(adrenocorticotropin/beta-lipotropin/alpha-melanocyte stimulatinghormone/beta-melanocyte stimulating hormone/beta-endorphin) (POMC),transcript variant 2; mitogen-activated protein kinase-activated proteinkinase 5 (MAPKAPK5), transcript variant 1; DnaJ homolog subfamily Cmember 8; ankyrin repeat and KH domain containing 1 (ANKHD1), transcriptvariant 3; mitochondrial ribosomal protein L34 (MRPL34), nuclear geneencoding mitochondrial protein; tripartite motif-containing 21 (TRIM21);four and a half LIM domains 1 (FHL1); tripartite motif-containing 21(TRIM21); four and a half LIM domains 1 (FHL1); xylosylprotein beta1,4-galactosyltransferase, polypeptide 7 (galactosyltransferase I)(B4GALT7); vacuolar protein sorting 37 homolog C (S. cerevisiae)(VPS37C); myotilin (MYOT); cDNA clone MGC:40426 IMAGE:5178085, completecds; Rap guanine nucleotide exchange factor 4 (RAPGEF4); Nucleolar andspindle-associated protein 1; tumor protein p53 inducible protein 3(TP53I3), transcript variant 1; Serine/threonine-protein kinase 12;additional sex combs like 1 (ASXL1); vaccinia related kinase 1 (VRK1);intercellular adhesion molecule 4 (ICAM4), transcript variant 1; caseinkinase 2, alpha prime polypeptide (CSNK2A2); ribosomal protein L41(RPL41), transcript variant 1; cDNA clone MGC:27376 IMAGE:4688477,complete eds; peptidyl arginine deiminase, type IV (PADI4); Signalrecognition particle 19 kDa protein; fibroblast growth factor 12(FGF12); Coiled-coil domain-containing protein 28A; fibroblast growthfactor 12 (FGF12), transcript variant 1; Golgi-associated plantpathogenesis-related protein 1; ubiquitin-conjugating enzyme E2S(UBE2S); 60S ribosomal protein L22; WD repeat domain 5 (WDR5),transcript variant 1; immunoglobulin heavy constant gamma 3 (G3m marker)(IGHG3); cyclic AMP phosphoprotein, 19 kD (ARPP-19); cDNA cloneMGC:31944 IMAGE:4878869 complete cds; coiled-coil domain containing 72(CCDC72); chemokine (C-C motif) ligand 19 (CCL19); immunoglobulin lambdaconstant 1 (IGLC1); Serine/threonine-protein kinase 6; serpin peptidaseinhibitor, clade E (nexin, plasminogen activator inhibitor type 1),member 2 (SERPINE2); FACT complex subunit SPT16; eukaryotic translationinitiation factor 1A, Y-linked (EIF1AY); protein (peptidylprolylcis/trans isomerase) NIMA-interacting, 4 (parvulin) (PIN4); elongationfactor 1 homolog (ELOF1); RNA (guanine-9-)-methyltransferasedomain-containing protein 3; Cyclin-dependent kinase-like 1; and MAPkinase-activated protein kinase
 3. 8. The method of claim 7, furtherwherein the presence of at least one immunocomplex between theautoantibodies in the biological sample targeting said additionalautoantigens is detected.
 9. The method of claim 4 wherein the substrateis a nitrocellulose-coated glass slide.
 10. The method of claim 1,wherein the presence of immunocomplexes between autoantibodies targetingcentaurin, alpha 2 (CENTA 2), and at least two additional autoantigensselected from the group consisting of jumonji domain containing 2D(JMJD2D); pentatricopeptide repeat domain 2 (PTCD2); lectin,galactoside-binding, soluble, 1 (galectin 1 or LGALS1); and regulatingsynaptic membrane exocytosis 4 (RIMS4) is detected.
 11. The method ofclaim 10, wherein the presence of immunocomplexes between autoantibodiestargeting centaurin, alpha 2 (CENTA 2), jumonji domain containing 2D(JMJD2D); pentatricopeptide repeat domain 2 (PTCD2); and lectin,galactoside-binding, soluble, 1 (galectin 1) (LGALS1) is detected. 12.The method of claim 10, wherein the presence of immunocomplexes betweenautoantibodies targeting centaurin, alpha 2 (CENTA 2), jumonji domaincontaining 2D (JMJD2D); pentatricopeptide repeat domain 2 (PTCD2); andregulating synaptic membrane exocytosis 4 (RIMS4) is detected.
 13. Amethod of generating a subject-specific, neurodegenerativedisease-specific autoantibody profile comprising: (a) obtaining animmunoglobulin-containing biological sample from a subject, (b)performing an assay on said biological sample to determine the presenceof more than one neurodegenerative disease diagnostic autoantibodies inthe biological sample, wherein said assay comprises the steps of: (i)forming immunocomplexes between autoantibodies targeting at least twoautoantigens selected from the group consisting of centaurin, alpha 2(CENTA 2), jumonji domain containing 2D (JMJD2D); pentatricopeptiderepeat domain 2 (PTCD2); lectin, galactoside-binding, soluble, 1(galectin 1)(LGALS1); and regulating synaptic membrane exocytosis 4(RIMS4); (ii) detecting the presence of said immunocomplexes, and (c)generating a subject-specific neurodegenerative disease-specificautoantibody profile of the autoantibodies present in the sample.